rs72552027

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001037.5(SCN1B):c.28G>A(p.Gly10Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000501 in 968,158 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 6 hom., cov: 31)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

SCN1B
NM_001037.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:8

Conservation

PhyloP100: -0.213

Variant links:

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]

SCN1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0072039366).

BP6

Variant 19-35030848-G-A is Benign according to our data. Variant chr19-35030848-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 190869.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=5, Benign=2, Uncertain_significance=2}. Variant chr19-35030848-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00223 (334/149682) while in subpopulation AFR AF= 0.00771 (318/41254). AF 95% confidence interval is 0.00701. There are 6 homozygotes in gnomad4. There are 161 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 334 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN1B	NM_001037.5 link	c.28G>A	p.Gly10Ser	missense_variant	Exon 1 of 6	ENST00000262631.11	NP_001028.1	Q07699-1
SCN1B	NM_199037.5 link	c.28G>A	p.Gly10Ser	missense_variant	Exon 1 of 3		NP_950238.1	Q07699-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCN1B	ENST00000262631.11 link	c.28G>A	p.Gly10Ser	missense_variant	Exon 1 of 6	1	NM_001037.5	ENSP00000262631.3	Q07699-1
SCN1B	ENST00000415950.5 link	c.28G>A	p.Gly10Ser	missense_variant	Exon 1 of 3	1		ENSP00000396915.2	Q07699-2
SCN1B	ENST00000638536.1 link	c.28G>A	p.Gly10Ser	missense_variant	Exon 1 of 5	1		ENSP00000492022.1	Q07699-1
SCN1B	ENST00000595652.5 link	c.28G>A	p.Gly10Ser	missense_variant	Exon 1 of 6	2		ENSP00000468848.1	B4DI92

Frequencies

GnomAD3 genomes

AF:

0.00222

AC:

332

AN:

149576

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00768

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000864

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00145

GnomAD3 exomes

AF:

0.00169

AC:

AN:

592

Hom.:

AF XY:

0.00267

AC XY:

AN XY:

374

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00962

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000184

AC:

151

AN:

818476

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

AN XY:

392200

show subpopulations

Gnomad4 AFR exome

AF:

0.00876

Gnomad4 AMR exome

AF:

0.000689

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000282

Gnomad4 OTH exome

AF:

0.000302

GnomAD4 genome

AF:

0.00223

AC:

334

AN:

149682

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

161

AN XY:

73042

show subpopulations

Gnomad4 AFR

AF:

0.00771

Gnomad4 AMR

AF:

0.000862

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00144

Alfa

AF:

0.000143

Hom.:

ExAC

AF:

0.0000556

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:8

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Jun 17, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: The SCN1B c.28G>A (p.Gly10Ser) variant involves the alteration of a non-conserved nucleotide, is not located in a known functional domain, and 2/4 in silico tools predict a benign outcome (SNPs&GO not captured due to low reliability index). This variant was found in 16/5008 control chromosomes, predominantly observed in the African subpopulation (16/1322 African alleles from 1000G; 0.01210). This frequency is significantly greater than the estimated maximal expected allele frequency of a pathogenic SCN1B variant (0.00001), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. However, the site is covered in fewer than 80% of the individuals in ExAC, which may indicate a low-quality site. The variant was identified in one SIDS case (also found in healthy African American adult control) and one LQTS patient without evidence of causality (i.e. co-segregation). In addition, one clinical diagnostic laboratory classified this variant as a VUS. Taken together and based on the allele frequency in the African subpopulation, this variant is classified as Likely Benign until additional information is available. -

Jan 31, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 02, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Reported in one African American infant with sudden infant death sydnrome (SIDS) and in one healthy, ethnically-matched control individual (Tan et al., 2010); Reported in one patient with LQTS (Rurio et al., 2014); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24662403, 20226894) -

not specified

Uncertain:1Benign:1

Dec 15, 2016

Athena Diagnostics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 13, 2016

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Brugada syndrome 5

Benign:2

Apr 28, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

SCN1B-related disorder

Benign:1

Nov 22, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Generalized epilepsy with febrile seizures plus, type 1

Benign:1

Apr 28, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Cardiovascular phenotype

Benign:1

Dec 14, 2018

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.068

T;T;.;.

Eigen

Benign

0.017

Eigen_PC

Benign

-0.050

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.51

.;T;T;T

MetaRNN

Benign

0.0072

T;T;T;T

MetaSVM

Uncertain

0.57

MutationAssessor

Benign

0.0

N;N;N;.

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.65

N;.;N;.

REVEL

Benign

0.25

Sift

Benign

0.36

T;.;D;.

Sift4G

Benign

0.40

T;.;T;T

Polyphen

1.0

D;D;D;D

Vest4

0.094

MutPred

0.36

Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);

MVP

0.97

MPC

0.67

ClinPred

0.11

GERP RS

2.0

Varity_R

0.067

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over