rs1135401736
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_001037.5(SCN1B):āc.373C>Gā(p.Arg125Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
SCN1B
NM_001037.5 missense
NM_001037.5 missense
Scores
9
9
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.66
Genes affected
SCN1B (HGNC:10586): (sodium voltage-gated channel beta subunit 1) Voltage-gated sodium channels are heteromeric proteins that function in the generation and propagation of action potentials in muscle and neuronal cells. They are composed of one alpha and two beta subunits, where the alpha subunit provides channel activity and the beta-1 subunit modulates the kinetics of channel inactivation. This gene encodes a sodium channel beta-1 subunit. Mutations in this gene result in generalized epilepsy with febrile seizures plus, Brugada syndrome 5, and defects in cardiac conduction. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
In a domain Ig-like C2-type (size 128) in uniprot entity SCN1B_HUMAN there are 7 pathogenic changes around while only 3 benign (70%) in NM_001037.5
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.965
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| SCN1B | NM_001037.5 | c.373C>G | p.Arg125Gly | missense_variant | Exon 3 of 6 | ENST00000262631.11 | NP_001028.1 | |
| SCN1B | NM_199037.5 | c.373C>G | p.Arg125Gly | missense_variant | Exon 3 of 3 | NP_950238.1 | ||
| SCN1B | NM_001321605.2 | c.274C>G | p.Arg92Gly | missense_variant | Exon 3 of 6 | NP_001308534.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461894Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727248
GnomAD4 exome
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2
AN:
1461894
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Cov.:
33
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0
AN XY:
727248
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
EpiCase
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EpiControl
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;M;.;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;D;.;.
REVEL
Pathogenic
Sift
Pathogenic
D;.;D;.;.
Sift4G
Uncertain
D;.;D;.;.
Polyphen
D;D;D;.;.
Vest4
MutPred
Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;.;
MVP
MPC
1.9
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.