19-35030843-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001037.5(SCN1B):c.23T>C(p.Val8Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,007,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V8L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SCN1B
NM_001037.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: -0.156

Publications

2 publications found

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:

HPN-AS1 (HGNC:47041): (HPN antisense RNA 1)

HPN-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21743363).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN1B	NM_001037.5	MANE Select	c.23T>C	p.Val8Ala	missense	Exon 1 of 6	NP_001028.1
	SCN1B	NM_199037.5		c.23T>C	p.Val8Ala	missense	Exon 1 of 3	NP_950238.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SCN1B	ENST00000262631.11	TSL:1 MANE Select	c.23T>C	p.Val8Ala	missense	Exon 1 of 6	ENSP00000262631.3
SCN1B	ENST00000415950.5	TSL:1	c.23T>C	p.Val8Ala	missense	Exon 1 of 3	ENSP00000396915.2
SCN1B	ENST00000638536.1	TSL:1	c.23T>C	p.Val8Ala	missense	Exon 1 of 5	ENSP00000492022.1

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

148506

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000449

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000105

AC:

AN:

858512

Hom.:

Cov.:

AF XY:

0.0000121

AC XY:

AN XY:

413890

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16164

American (AMR)

AF:

0.00

AC:

AN:

4770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8542

East Asian (EAS)

AF:

0.00

AC:

AN:

12288

South Asian (SAS)

AF:

0.00

AC:

AN:

29184

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2054

European-Non Finnish (NFE)

AF:

0.0000122

AC:

AN:

738884

Other (OTH)

AF:

0.00

AC:

AN:

31210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000269

AC:

AN:

148506

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

72384

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40732

American (AMR)

AF:

0.00

AC:

AN:

15016

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3422

East Asian (EAS)

AF:

0.00

AC:

AN:

4944

South Asian (SAS)

AF:

0.00

AC:

AN:

4784

European-Finnish (FIN)

AF:

0.000104

AC:

AN:

9600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.0000449

AC:

AN:

66752

Other (OTH)

AF:

0.00

AC:

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Brugada syndrome 5

Uncertain:1

Jun 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 8 of the SCN1B protein (p.Val8Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with SCN1B-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 190868). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

not provided

Uncertain:1

Nov 11, 2024

GeneDx

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria.

Cardiovascular phenotype

Uncertain:1

Aug 26, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.V8A variant (also known as c.23T>C), located in coding exon 1 of the SCN1B gene, results from a T to C substitution at nucleotide position 23. The valine at codon 8 is replaced by alanine, an amino acid with similar properties. This variant was reported in individual(s) with features consistent with epilepsy (Truty R et al. Epilepsia Open. 2019 Sep;4(3):397-408). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.38

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.22

MetaSVM

Uncertain

0.093

MutationAssessor

Benign

0.0

PhyloP100

-0.16

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.76

REVEL

Benign

0.29

Sift

Benign

0.17

Sift4G

Benign

0.37

Polyphen

0.019

Vest4

0.085

MutPred

0.34

Loss of sheet (P = 0.0228)

MVP

0.88

MPC

0.81

ClinPred

0.078

GERP RS

2.0

PromoterAI

0.080

Neutral

(source)

Varity_R

0.091

gMVP

0.55

Mutation Taster

=81/19

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over