rs140949982

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001037.5(SCN1B):c.267C>T(p.Arg89Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00042 in 1,614,046 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

SCN1B
NM_001037.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -4.69

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 19-35033558-C-T is Benign according to our data. Variant chr19-35033558-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 138992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-35033558-C-T is described in Lovd as [Benign]. Variant chr19-35033558-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-4.69 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00208 (317/152218) while in subpopulation AFR AF= 0.00739 (307/41528). AF 95% confidence interval is 0.00671. There are 2 homozygotes in gnomad4. There are 142 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 317 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN1B	NM_001037.5 link	c.267C>T	p.Arg89Arg	synonymous_variant	Exon 3 of 6	ENST00000262631.11	NP_001028.1	Q07699-1
SCN1B	NM_199037.5 link	c.267C>T	p.Arg89Arg	synonymous_variant	Exon 3 of 3		NP_950238.1	Q07699-2
SCN1B	NM_001321605.2 link	c.168C>T	p.Arg56Arg	synonymous_variant	Exon 3 of 6		NP_001308534.1	Q07699A0A1W2PR05

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN1B	ENST00000262631.11 link	c.267C>T	p.Arg89Arg	synonymous_variant	Exon 3 of 6	1	NM_001037.5	ENSP00000262631.3		Q07699-1

Frequencies

GnomAD3 genomes

AF:

0.00209

AC:

318

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00744

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000549

AC:

138

AN:

251358

Hom.:

AF XY:

0.000412

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00812

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000247

AC:

361

AN:

1461828

Hom.:

Cov.:

AF XY:

0.000223

AC XY:

162

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00935

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.00208

AC:

317

AN:

152218

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

142

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00739

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00124

Hom.:

Bravo

AF:

0.00247

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Dec 31, 2012

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Sep 01, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 02, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:4

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 16, 2016

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: The SCN1B c.267C>T (p.Arg89=) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 4/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. This variant was found in 85/121400 control chromosomes at a frequency of 0.0007002, which is approximately 70 times of the estimated maximal allele frequency of a pathogenic SCN1B variant (0.00001), suggesting this variant is a benign polymorphism. The variant was found to co-occure with a pathogenic variant, c.573_577delGCGCT in KCNH2, further suggesting non-pathogenic nature of the variant of interest. In addition, several clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as Benign. -

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SCN1B: BP4, BP7, BS2 -

Jun 30, 2022

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Brugada syndrome 5

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Generalized epilepsy with febrile seizures plus, type 1;C2748541:Brugada syndrome 5;C3809311:Atrial fibrillation, familial, 13;C4479236:Developmental and epileptic encephalopathy, 52

Benign:1

Jan 12, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

SCN1B-related disorder

Benign:1

Jul 16, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Cardiovascular phenotype

Benign:1

Jun 14, 2016

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

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.46

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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