MutationTaster - study a chromosomal position

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input seems to be ok - now mapping the variant to the different transcripts...
found 3 transcript(s)...
Querying Taster for transcript #1: ENST00000306071
Querying Taster for transcript #2: ENST00000536404
Querying Taster for transcript #3: ENST00000576360
MT speed 0 s - this script 4.429414 s

Results

genesymbol	prediction	probability	model	prediction problem	splicing	ClinVar	amino acid changes	variant type	dbSNP ID	protein length	file
CHRNB1	disease_causing_automatic	0.127985331701287	simple_aae		affected	0	L213M	single base exchange	rs137852811		show file
CHRNB1	disease_causing_automatic	0.205352110561329	simple_aae		affected	0	L285M	single base exchange	rs137852811		show file
CHRNB1	disease_causing_automatic	1	without_aae		affected	0		single base exchange	rs137852811		show file

Taster files

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.127985331701287 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM960296)
known disease mutation: rs18373 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr17:7357648C>AN/A show variant in all transcripts IGV

HGNC symbol

CHRNB1

Ensembl transcript ID

ENST00000536404

Genbank transcript ID

N/A

UniProt peptide

P11230

alteration type

single base exchange

alteration region

CDS

DNA changes

c.637C>A
cDNA.767C>A
g.9269C>A

AA changes

L213M Score: 15 explain score(s)

position(s) of altered AA
if AA alteration in CDS

213

frameshift

known variant

Reference ID: rs137852811
Allele 'A' was neither found in ExAC nor 1000G.
known disease mutation: rs18373 (pathogenic for Myasthenic syndrome, congenital, 2a, slow-channel) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM960296)

known disease mutation at this position, please check HGMD for details (HGMD ID CM960296)
known disease mutation at this position, please check HGMD for details (HGMD ID CM960296)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	2.193	1
	2.322	1
(flanking)	4.255	1

explain score(s) and/or inspect your position(s) in in UCSC Genome Browser

splice sites

effect	gDNA position	score	wt detection sequence	exon-intron border
Acc marginally increased	9266	wt: 0.5598 / mu: 0.5986 (marginal change - not scored)	wt: TGGGGCTCTCAATCTTTGCCCTGCTGACCCTTACTGTGTTC mu: TGGGGCTCTCAATCTTTGCCCTGATGACCCTTACTGTGTTC	gccc\|TGCT
Acc gained	9268	0.43	mu: GGGCTCTCAATCTTTGCCCTGATGACCCTTACTGTGTTCCT	cctg\|ATGA
Donor gained	9265	0.53	mu: TTTGCCCTGATGACC	TGCC\|ctga

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

213

mutated

all conserved

213

Ptroglodytes

all identical

ENSPTRG00000008689

285

Mmulatta

not conserved

ENSMMUG00000017690

285

Fcatus

no homologue

Mmusculus

all identical

ENSMUSG00000041189

285

Ggallus

no homologue

Trubripes

all conserved

ENSTRUG00000004322

278

Drerio

all conserved

ENSDARG00000022532

273

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

no homologue

protein features

start (aa)	end (aa)	feature	details
24	244	TOPO_DOM	Extracellular (Potential).	lost
245	269	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
277	295	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
311	332	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
333	469	TOPO_DOM	Cytoplasmic (Potential).	might get lost (downstream of altered splice site)
390	390	MOD_RES	Phosphotyrosine; by Tyr-kinases (By similarity).	might get lost (downstream of altered splice site)
470	488	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1290 / 1290

position (AA) of stopcodon in wt / mu AA sequence

430 / 430

position of stopcodon in wt / mu cDNA

1420 / 1420

poly(A) signal

N/A

conservation
nucleotide level for all changes - no scoring up to now

N/A

position of start ATG in wt / mu cDNA

131 / 131

chromosome

strand

last intron/exon boundary

1280

theoretical NMD boundary in CDS

1099

length of CDS

1290

coding sequence (CDS) position

637

cDNA position
(for ins/del: last normal base / first normal base)

767

gDNA position
(for ins/del: last normal base / first normal base)

9269

chromosomal position
(for ins/del: last normal base / first normal base)

7357648

original gDNA sequence snippet

GGCTCTCAATCTTTGCCCTGCTGACCCTTACTGTGTTCCTG

altered gDNA sequence snippet

GGCTCTCAATCTTTGCCCTGATGACCCTTACTGTGTTCCTG

original cDNA sequence snippet

GGCTCTCAATCTTTGCCCTGCTGACCCTTACTGTGTTCCTG

altered cDNA sequence snippet

GGCTCTCAATCTTTGCCCTGATGACCCTTACTGTGTTCCTG

wildtype AA sequence

MSTKVYLDLE WTDYRLSWDP AEHDGIDSLR ITAESVWLPD VVLLNNNDGN FDVALDISVV
VSSDGSVRWQ PPGIYRSSCS IQVTYFPFDW QNCTMVFSSY SYDSSEVSLQ TGLGPDGQGH
QEIHIHEGTF IENGQWEIIH KPSRLIQPPG DPRGGREGQR QEVIFYLIIR RKPLFYLVNV
IAPCILITLL AIFVFYLPPD AGEKMGLSIF ALLTLTVFLL LLADKVPETS LSVPIIIKYL
MFTMVLVTFS VILSVVVLNL HHRSPHTHQM PLWVRQIFIH KLPLYLRLKR PKPERDLMPE
PPHCSSPGSG WGRGTDEYFI RKPPSDFLFP KPNRFQPELS APDLRRFIDG PNRAVALLPE
LREVVSSISY IARQLQEQED HDALKEDWQF VAMVVDRLFL WTFIIFTSVG TLVIFLDATY
HLPPPDPFP*

mutated AA sequence

MSTKVYLDLE WTDYRLSWDP AEHDGIDSLR ITAESVWLPD VVLLNNNDGN FDVALDISVV
VSSDGSVRWQ PPGIYRSSCS IQVTYFPFDW QNCTMVFSSY SYDSSEVSLQ TGLGPDGQGH
QEIHIHEGTF IENGQWEIIH KPSRLIQPPG DPRGGREGQR QEVIFYLIIR RKPLFYLVNV
IAPCILITLL AIFVFYLPPD AGEKMGLSIF ALMTLTVFLL LLADKVPETS LSVPIIIKYL
MFTMVLVTFS VILSVVVLNL HHRSPHTHQM PLWVRQIFIH KLPLYLRLKR PKPERDLMPE
PPHCSSPGSG WGRGTDEYFI RKPPSDFLFP KPNRFQPELS APDLRRFIDG PNRAVALLPE
LREVVSSISY IARQLQEQED HDALKEDWQF VAMVVDRLFL WTFIIFTSVG TLVIFLDATY
HLPPPDPFP*

speed

0.48 s

All positions are in basepairs (bp) if not explicitly stated differently.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project
back to results table

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.205352110561329 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM960296)
known disease mutation: rs18373 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr17:7357648C>AN/A show variant in all transcripts IGV

HGNC symbol

CHRNB1

Ensembl transcript ID

ENST00000306071

Genbank transcript ID

NM_000747

UniProt peptide

P11230

alteration type

single base exchange

alteration region

CDS

DNA changes

c.853C>A
cDNA.920C>A
g.9269C>A

AA changes

L285M Score: 15 explain score(s)

position(s) of altered AA
if AA alteration in CDS

285

frameshift

known variant

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	2.193	1
	2.322	1
(flanking)	4.255	1

explain score(s) and/or inspect your position(s) in in UCSC Genome Browser

splice sites

effect	gDNA position	score	wt detection sequence	exon-intron border
Acc marginally increased	9266	wt: 0.5598 / mu: 0.5986 (marginal change - not scored)	wt: TGGGGCTCTCAATCTTTGCCCTGCTGACCCTTACTGTGTTC mu: TGGGGCTCTCAATCTTTGCCCTGATGACCCTTACTGTGTTC	gccc\|TGCT
Acc gained	9268	0.43	mu: GGGCTCTCAATCTTTGCCCTGATGACCCTTACTGTGTTCCT	cctg\|ATGA
Donor gained	9265	0.53	mu: TTTGCCCTGATGACC	TGCC\|ctga

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

285

mutated

all conserved

285

Ptroglodytes

all identical

ENSPTRG00000008689

285

Mmulatta

not conserved

ENSMMUG00000017690

285

Fcatus

no homologue

Mmusculus

all identical

ENSMUSG00000041189

285

Ggallus

no homologue

Trubripes

all conserved

ENSTRUG00000004322

278

Drerio

all conserved

ENSDARG00000022532

273

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

no homologue

protein features

start (aa)	end (aa)	feature	details
277	295	TRANSMEM	Helical; (Potential).	lost
311	332	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
333	469	TOPO_DOM	Cytoplasmic (Potential).	might get lost (downstream of altered splice site)
390	390	MOD_RES	Phosphotyrosine; by Tyr-kinases (By similarity).	might get lost (downstream of altered splice site)
470	488	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1506 / 1506

position (AA) of stopcodon in wt / mu AA sequence

502 / 502

position of stopcodon in wt / mu cDNA

1573 / 1573

poly(A) signal

N/A

conservation
nucleotide level for all changes - no scoring up to now

N/A

position of start ATG in wt / mu cDNA

68 / 68

chromosome

strand

last intron/exon boundary

1433

theoretical NMD boundary in CDS

1315

length of CDS

1506

coding sequence (CDS) position

853

cDNA position
(for ins/del: last normal base / first normal base)

920

gDNA position
(for ins/del: last normal base / first normal base)

9269

chromosomal position
(for ins/del: last normal base / first normal base)

7357648

original gDNA sequence snippet

GGCTCTCAATCTTTGCCCTGCTGACCCTTACTGTGTTCCTG

altered gDNA sequence snippet

GGCTCTCAATCTTTGCCCTGATGACCCTTACTGTGTTCCTG

original cDNA sequence snippet

GGCTCTCAATCTTTGCCCTGCTGACCCTTACTGTGTTCCTG

altered cDNA sequence snippet

GGCTCTCAATCTTTGCCCTGATGACCCTTACTGTGTTCCTG

wildtype AA sequence

MTPGALLMLL GALGAPLAPG VRGSEAEGRL REKLFSGYDS SVRPAREVGD RVRVSVGLIL
AQLISLNEKD EEMSTKVYLD LEWTDYRLSW DPAEHDGIDS LRITAESVWL PDVVLLNNND
GNFDVALDIS VVVSSDGSVR WQPPGIYRSS CSIQVTYFPF DWQNCTMVFS SYSYDSSEVS
LQTGLGPDGQ GHQEIHIHEG TFIENGQWEI IHKPSRLIQP PGDPRGGREG QRQEVIFYLI
IRRKPLFYLV NVIAPCILIT LLAIFVFYLP PDAGEKMGLS IFALLTLTVF LLLLADKVPE
TSLSVPIIIK YLMFTMVLVT FSVILSVVVL NLHHRSPHTH QMPLWVRQIF IHKLPLYLRL
KRPKPERDLM PEPPHCSSPG SGWGRGTDEY FIRKPPSDFL FPKPNRFQPE LSAPDLRRFI
DGPNRAVALL PELREVVSSI SYIARQLQEQ EDHDALKEDW QFVAMVVDRL FLWTFIIFTS
VGTLVIFLDA TYHLPPPDPF P*

mutated AA sequence

MTPGALLMLL GALGAPLAPG VRGSEAEGRL REKLFSGYDS SVRPAREVGD RVRVSVGLIL
AQLISLNEKD EEMSTKVYLD LEWTDYRLSW DPAEHDGIDS LRITAESVWL PDVVLLNNND
GNFDVALDIS VVVSSDGSVR WQPPGIYRSS CSIQVTYFPF DWQNCTMVFS SYSYDSSEVS
LQTGLGPDGQ GHQEIHIHEG TFIENGQWEI IHKPSRLIQP PGDPRGGREG QRQEVIFYLI
IRRKPLFYLV NVIAPCILIT LLAIFVFYLP PDAGEKMGLS IFALMTLTVF LLLLADKVPE
TSLSVPIIIK YLMFTMVLVT FSVILSVVVL NLHHRSPHTH QMPLWVRQIF IHKLPLYLRL
KRPKPERDLM PEPPHCSSPG SGWGRGTDEY FIRKPPSDFL FPKPNRFQPE LSAPDLRRFI
DGPNRAVALL PELREVVSSI SYIARQLQEQ EDHDALKEDW QFVAMVVDRL FLWTFIIFTS
VGTLVIFLDA TYHLPPPDPF P*

speed

1.34 s

mutation t@sting

documentation

Prediction

disease causing

Model: without_aae, prob: 1 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

known disease mutation at this position (HGMD CM960296)
known disease mutation: rs18373 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr17:7357648C>AN/A show variant in all transcripts IGV

HGNC symbol

CHRNB1

Ensembl transcript ID

ENST00000576360

Genbank transcript ID

N/A

UniProt peptide

P11230

alteration type

single base exchange

alteration region

intron

DNA changes

g.9269C>A

AA changes

N/A

position(s) of altered AA
if AA alteration in CDS

N/A

frameshift

N/A

known variant

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	2.193	1
	2.322	1
(flanking)	4.255	1

explain score(s) and/or inspect your position(s) in in UCSC Genome Browser

splice sites

effect	gDNA position	score	wt detection sequence	exon-intron border
Acc marginally increased	9266	wt: 0.5598 / mu: 0.5986 (marginal change - not scored)	wt: TGGGGCTCTCAATCTTTGCCCTGCTGACCCTTACTGTGTTC mu: TGGGGCTCTCAATCTTTGCCCTGATGACCCTTACTGTGTTC	gccc\|TGCT
Acc gained	9268	0.43	mu: GGGCTCTCAATCTTTGCCCTGATGACCCTTACTGTGTTCCT	cctg\|ATGA
Donor gained	9265	0.53	mu: TTTGCCCTGATGACC	TGCC\|ctga

distance from splice site

115

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

N/A

protein features

start (aa)	end (aa)	feature	details
24	244	TOPO_DOM	Extracellular (Potential).	might get lost (downstream of altered splice site)
210	210	CONFLICT	I -> N (in Ref. 1; CAA32939).	might get lost (downstream of altered splice site)
245	269	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
277	295	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
311	332	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
333	469	TOPO_DOM	Cytoplasmic (Potential).	might get lost (downstream of altered splice site)
390	390	MOD_RES	Phosphotyrosine; by Tyr-kinases (By similarity).	might get lost (downstream of altered splice site)
470	488	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)

length of protein

N/A

AA sequence altered

N/A

position of stopcodon in wt / mu CDS

N/A

position (AA) of stopcodon in wt / mu AA sequence

N/A

position of stopcodon in wt / mu cDNA

N/A

poly(A) signal

N/A

conservation
nucleotide level for all changes - no scoring up to now

N/A

position of start ATG in wt / mu cDNA

103 / 103

chromosome

strand

last intron/exon boundary

1105

theoretical NMD boundary in CDS

952

length of CDS

1143

coding sequence (CDS) position

N/A

cDNA position
(for ins/del: last normal base / first normal base)

N/A

gDNA position
(for ins/del: last normal base / first normal base)

9269

chromosomal position
(for ins/del: last normal base / first normal base)

7357648

original gDNA sequence snippet

GGCTCTCAATCTTTGCCCTGCTGACCCTTACTGTGTTCCTG

altered gDNA sequence snippet

GGCTCTCAATCTTTGCCCTGATGACCCTTACTGTGTTCCTG

original cDNA sequence snippet

N/A

altered cDNA sequence snippet

N/A

wildtype AA sequence

MSTKVYLDLE WTDYRLSWDP AEHDGIDSLR ITAESVWLPD VVLLNNNDGN FDVALDISVV
VSSDGSVRWQ PPGIYRSSCS IQVTYFPFDW QNCTMVFSSY SYDSSEVSLQ TGLGPDGQGH
QEIHIHEGTF IENGQWEIIH KPSRLIQPPG DPRGGREGQR QEVIFYLIIR RKPLFYLVNV
IAPCILITLL AIFVFYLPPD AVILSVVVLN LHHRSPHTHQ MPLWVRQIFI HKLPLYLRLK
RPKPERDLMP EPPHCSSPGS GWGRGTDEYF IRKPPSDFLF PKPNRFQPEL SAPDLRRFID
GPNRAVALLP ELREVVSSIS YIARQLQEQE DHDALKEDWQ FVAMVVDRLF LWTFIIFTSV
GTLVIFLDAT YHLPPPDPFP *

mutated AA sequence

N/A

speed

1.04 s

MutationTaster - study a chromosomal position

Results

Taster files

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

mutation t@sting

Prediction

disease causing

Problems