ENST00000415950.5:c.749G>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000415950.5(SCN1B):c.749G>C(p.Arg250Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,549,996 control chromosomes in the GnomAD database, including 16,715 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R250K) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.13 ( 1462 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15253 hom. )

Consequence

SCN1B
ENST00000415950.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

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=0.0036869943).

BP6

Variant 19-35034040-G-C is Benign according to our data. Variant chr19-35034040-G-C is described in ClinVar as [Benign]. Clinvar id is 36756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-35034040-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN1B	NM_001037.5 link	c.448+301G>C		intron_variant	Intron 3 of 5	ENST00000262631.11	NP_001028.1	Q07699-1
SCN1B	NM_199037.5 link	c.749G>C	p.Arg250Thr	missense_variant	Exon 3 of 3		NP_950238.1	Q07699-2
SCN1B	NM_001321605.2 link	c.349+301G>C		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>C		intron_variant	Intron 3 of 5	1	NM_001037.5	ENSP00000262631.3		Q07699-1

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20133

AN:

151974

Hom.:

1465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0634

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.259

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.166

GnomAD3 exomes

AF:

0.144

AC:

22249

AN:

154732

Hom.:

1785

AF XY:

0.144

AC XY:

11794

AN XY:

81752

show subpopulations

Gnomad AFR exome

AF:

0.0617

Gnomad AMR exome

AF:

0.0872

Gnomad ASJ exome

AF:

0.256

Gnomad EAS exome

AF:

0.213

Gnomad SAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.183

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.156

GnomAD4 exome

AF:

0.143

AC:

199879

AN:

1397904

Hom.:

15253

Cov.:

AF XY:

0.144

AC XY:

98954

AN XY:

689562

show subpopulations

Gnomad4 AFR exome

AF:

0.0596

Gnomad4 AMR exome

AF:

0.0925

Gnomad4 ASJ exome

AF:

0.263

Gnomad4 EAS exome

AF:

0.195

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.180

Gnomad4 NFE exome

AF:

0.142

Gnomad4 OTH exome

AF:

0.154

GnomAD4 genome

AF:

0.132

AC:

20122

AN:

152092

Hom.:

1462

Cov.:

AF XY:

0.134

AC XY:

9993

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0633

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.259

Gnomad4 EAS

AF:

0.198

Gnomad4 SAS

AF:

0.112

Gnomad4 FIN

AF:

0.189

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.164

Alfa

AF:

0.122

Hom.:

298

Bravo

AF:

0.127

TwinsUK

AF:

0.132

AC:

490

ALSPAC

AF:

0.146

AC:

561

ESP6500AA

AF:

0.0602

AC:

136

ESP6500EA

AF:

0.145

AC:

639

ExAC

AF:

0.0970

AC:

3853

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 22, 2013

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. -

Jun 24, 2013

Biesecker Lab/Clinical Genomics Section, National Institutes of Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Jul 31, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 29. Only high quality variants are reported. -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Brugada syndrome 5

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Cardiac arrhythmia

Benign:1

Apr 22, 2013

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.93

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.41

T;T

MetaRNN

Benign

0.0037

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

0.010

N;.

REVEL

Benign

0.047

Sift

Pathogenic

0.0

D;.

Polyphen

0.22

B;.

Vest4

0.096

MPC

1.4

ClinPred

0.013

GERP RS

1.8

gMVP

0.28

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