Variant rs1060499899 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000415950.5(SCN1B):c.577G>A(p.Glu193Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000756 in 1,455,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E193G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

SCN1B
ENST00000415950.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.15

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10996118).

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SCN1B	NM_001037.5 linkuse as main transcript	c.448+129G>A		intron_variant		ENST00000262631.11
SCN1B	NM_199037.5 linkuse as main transcript	c.577G>A	p.Glu193Lys	missense_variant	3/3
SCN1B	NM_001321605.2 linkuse as main transcript	c.349+129G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN1B	ENST00000262631.11 linkuse as main transcript	c.448+129G>A		intron_variant		1	NM_001037.5	P1	Q07699-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000423

AC:

AN:

236404

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128766

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:

0.00000944

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000756

AC:

AN:

1455638

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723424

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:

0.00000992

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000472

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

3.4

DANN

Benign

0.092

Eigen

Benign

-0.90

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.37

T;T

M_CAP

Benign

0.054

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.69

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.25

N;.

REVEL

Benign

0.10

Sift

Benign

0.082

T;.

Sift4G

Benign

0.14

T;.

Polyphen

0.0030

B;.

Vest4

0.088

MutPred

0.33

Loss of sheet (P = 0.0025);.;

MVP

0.61

MPC

0.76

ClinPred

0.040

GERP RS

0.66

gMVP

0.29

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over