Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001037.5(SCN1B):c.29G>A(p.Gly10Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000123 in 813,306 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G10S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

SCN1B
NM_001037.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0420

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.29G>A	p.Gly10Asp	missense	Exon 1 of 6	NP_001028.1
	SCN1B	NM_199037.5		c.29G>A	p.Gly10Asp	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.29G>A	p.Gly10Asp	missense	Exon 1 of 6	ENSP00000262631.3
SCN1B	ENST00000415950.5	TSL:1	c.29G>A	p.Gly10Asp	missense	Exon 1 of 3	ENSP00000396915.2
SCN1B	ENST00000638536.1	TSL:1	c.29G>A	p.Gly10Asp	missense	Exon 1 of 5	ENSP00000492022.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000123

AC:

AN:

813306

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

389904

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

15544

American (AMR)

AF:

0.00

AC:

AN:

4358

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7974

East Asian (EAS)

AF:

0.00

AC:

AN:

12134

South Asian (SAS)

AF:

0.00

AC:

AN:

21964

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1938

European-Non Finnish (NFE)

AF:

0.00000142

AC:

AN:

705492

Other (OTH)

AF:

0.00

AC:

AN:

29684

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

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

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Brugada syndrome 5 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.43

M_CAP

Pathogenic

0.97

MetaRNN

Uncertain

0.60

MetaSVM

Uncertain

0.67

MutationAssessor

Benign

0.0

PhyloP100

0.042

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.61

Sift

Benign

0.15

Sift4G

Benign

0.21

Polyphen

0.99

Vest4

0.42

MutPred

0.49

Loss of sheet (P = 0.0457)

MVP

0.98

MPC

0.87

ClinPred

0.38

GERP RS

3.2

PromoterAI

0.077

Neutral

(source)

Varity_R

0.14

gMVP

0.69

Mutation Taster

=83/17

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.

19-35030849-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over