rs67486287

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_199037.5(SCN1B):c.749G>A(p.Arg250Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000361 in 1,550,376 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R250T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 6 hom. )

Consequence

SCN1B
NM_199037.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.409

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056346953).

BP6

Variant 19-35034040-G-A is Benign according to our data. Variant chr19-35034040-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 139000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-35034040-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00023 (35/152124) while in subpopulation SAS AF= 0.00355 (17/4786). AF 95% confidence interval is 0.00226. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN1B	NM_001037.5 link	c.448+301G>A		intron_variant	Intron 3 of 5	ENST00000262631.11	NP_001028.1	Q07699-1
SCN1B	NM_199037.5 link	c.749G>A	p.Arg250Lys	missense_variant	Exon 3 of 3		NP_950238.1	Q07699-2
SCN1B	NM_001321605.2 link	c.349+301G>A		intron_variant	Intron 3 of 5		NP_001308534.1	Q07699A0A1W2PR05

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN1B	ENST00000262631.11 link	c.448+301G>A		intron_variant	Intron 3 of 5	1	NM_001037.5	ENSP00000262631.3		Q07699-1

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00355

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000795

AC:

123

AN:

154732

Hom.:

AF XY:

0.00121

AC XY:

AN XY:

81752

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00509

Gnomad FIN exome

AF:

0.000131

Gnomad NFE exome

AF:

0.0000665

Gnomad OTH exome

AF:

0.000230

GnomAD4 exome

AF:

0.000375

AC:

524

AN:

1398252

Hom.:

Cov.:

AF XY:

0.000526

AC XY:

363

AN XY:

689732

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00496

Gnomad4 FIN exome

AF:

0.000304

Gnomad4 NFE exome

AF:

0.0000854

Gnomad4 OTH exome

AF:

0.000276

GnomAD4 genome

AF:

0.000230

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00355

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000400

Hom.:

298

ExAC

AF:

0.00128

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 04, 2014

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. -

Brugada syndrome 5

Benign:1

Dec 11, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Mar 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SCN1B: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.95

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.30

T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-0.70

PrimateAI

Benign

0.32

PROVEAN

Benign

0.040

N;.

REVEL

Benign

0.066

Sift

Pathogenic

0.0

D;.

Polyphen

0.0010

B;.

Vest4

0.13

MVP

0.84

MPC

0.81

ClinPred

0.047

GERP RS

1.8

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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