rs8100085

Positions:

• chr19-35032215-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001037.5(SCN1B):​c.41-313T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,074 control chromosomes in the GnomAD database, including 13,287 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.41 (13287 hom., cov: 32)
• Consequence: SCN1B NM_001037.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.78

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-35032215-T-A is Benign according to our data. Variant chr19-35032215-T-A is described in ClinVar as [Benign]. Clinvar id is 683808.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN1B	NM_001037.5	c.41-313T>A		intron_variant		ENST00000262631.11	NP_001028.1
SCN1B	NM_199037.5	c.41-313T>A		intron_variant			NP_950238.1
SCN1B	NM_001321605.2	c.-59-313T>A		intron_variant			NP_001308534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN1B	ENST00000262631.11	c.41-313T>A		intron_variant		1	NM_001037.5	ENSP00000262631.3

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62184 AN: 151954 Hom.: 13263 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.427

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.409 AC: 62248 AN: 152074 Hom.: 13287 Cov.: 32 AF XY: 0.408 AC XY: 30354 AN XY: 74318

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.428

Alfa AF: 0.404 Hom.: 1594

Bravo AF: 0.412

Asia WGS AF: 0.296 AC: 1029 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.61
DANN	Benign	0.69

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

Other links and lift over

dbSNP: rs8100085; hg19: chr19-35523119; COSMIC: COSV52895172; COSMIC: COSV52895172;