Variant rs746782800 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_001037.5(SCN1B):c.214C>G(p.Arg72Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,764 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SCN1B
NM_001037.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a disulfide_bond (size 81) in uniprot entity SCN1B_HUMAN there are 6 pathogenic changes around while only 1 benign (86%) in NM_001037.5

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35604382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN1B	NM_001037.5 linkuse as main transcript	c.214C>G	p.Arg72Gly	missense_variant	3/6	ENST00000262631.11	NP_001028.1	Q07699-1
SCN1B	NM_199037.5 linkuse as main transcript	c.214C>G	p.Arg72Gly	missense_variant	3/3		NP_950238.1	Q07699-2
SCN1B	NM_001321605.2 linkuse as main transcript	c.115C>G	p.Arg39Gly	missense_variant	3/6		NP_001308534.1	Q07699A0A1W2PR05

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN1B	ENST00000262631.11 linkuse as main transcript	c.214C>G	p.Arg72Gly	missense_variant	3/6	1	NM_001037.5	ENSP00000262631.3		Q07699-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251082

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135758

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461764

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Aug 11, 2023

Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

0.0027

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.16

T;T;.;.;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.85

.;T;T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.36

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;N;.;.

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.5

D;.;D;.;.

REVEL

Benign

0.18

Sift

Benign

0.42

T;.;T;.;.

Sift4G

Benign

0.34

T;.;T;.;.

Polyphen

0.98

D;D;D;.;.

Vest4

0.57

MutPred

0.59

Loss of stability (P = 0.0672);Loss of stability (P = 0.0672);Loss of stability (P = 0.0672);.;.;

MVP

0.62

MPC

0.86

ClinPred

0.56

GERP RS

4.5

Varity_R

0.33

gMVP

0.95

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