dbSNP rs786205834: SCN1B:p.Leu13Gln (chr19-35030858-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001037.5(SCN1B):c.38T>A(p.Leu13Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 721,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SCN1B
NM_001037.5 missense, splice_region

Scores

Splicing: ADA: 0.0002501

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0190

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40847212).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN1B	NM_001037.5 link	c.38T>A	p.Leu13Gln	missense_variant, splice_region_variant	Exon 1 of 6	ENST00000262631.11	NP_001028.1	Q07699-1
SCN1B	NM_199037.5 link	c.38T>A	p.Leu13Gln	missense_variant, splice_region_variant	Exon 1 of 3		NP_950238.1	Q07699-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCN1B	ENST00000262631.11 link	c.38T>A	p.Leu13Gln	missense_variant, splice_region_variant	Exon 1 of 6	1	NM_001037.5	ENSP00000262631.3	Q07699-1
SCN1B	ENST00000415950.5 link	c.38T>A	p.Leu13Gln	missense_variant, splice_region_variant	Exon 1 of 3	1		ENSP00000396915.2	Q07699-2
SCN1B	ENST00000638536.1 link	c.38T>A	p.Leu13Gln	missense_variant, splice_region_variant	Exon 1 of 5	1		ENSP00000492022.1	Q07699-1
SCN1B	ENST00000595652.5 link	c.38T>A	p.Leu13Gln	missense_variant, splice_region_variant	Exon 1 of 6	2		ENSP00000468848.1	B4DI92

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

721024

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

344252

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:

0.00000159

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.15

T;T;.;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.48

.;T;T;T

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.41

T;T;T;T

MetaSVM

Uncertain

0.73

MutationAssessor

Benign

0.0

N;N;N;.

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.9

N;.;N;.

REVEL

Pathogenic

0.70

Sift

Benign

0.14

T;.;D;.

Sift4G

Benign

0.20

T;.;D;T

Polyphen

0.84

P;P;D;P

Vest4

0.52

MutPred

0.52

Gain of loop (P = 0.0195);Gain of loop (P = 0.0195);Gain of loop (P = 0.0195);Gain of loop (P = 0.0195);

MVP

0.96

MPC

0.70

ClinPred

0.23

GERP RS

3.2

Varity_R

0.31

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00025

dbscSNV1_RF

Benign

0.0080

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over