rs2892992

Positions:

• chr2-166061933-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001165963.4(SCN1A):​c.265-3245A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,106 control chromosomes in the GnomAD database, including 3,495 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3495 hom., cov: 33)
• Consequence: SCN1A NM_001165963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

Genes affected

SCN1A (HGNC:10585): (sodium voltage-gated channel alpha subunit 1) Voltage-dependent sodium channels are heteromeric complexes that regulate sodium exchange between intracellular and extracellular spaces and are essential for the generation and propagation of action potentials in muscle cells and neurons. Each sodium channel is composed of a large pore-forming, glycosylated alpha subunit and two smaller beta subunits. This gene encodes a sodium channel alpha subunit, which has four homologous domains, each of which contains six transmembrane regions. Allelic variants of this gene are associated with generalized epilepsy with febrile seizures and epileptic encephalopathy. Alternative splicing results in multiple transcript variants. The RefSeq Project has decided to create four representative RefSeq records. Three of the transcript variants are supported by experimental evidence and the fourth contains alternate 5' untranslated exons, the exact combination of which have not been experimentally confirmed for the full-length transcript. [provided by RefSeq, Oct 2015]

SCN1A-AS1 (HGNC:54069): (SCN1A and SCN9A antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN1A	NM_001165963.4	c.265-3245A>T		intron_variant		ENST00000674923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN1A	ENST00000674923.1	c.265-3245A>T		intron_variant			NM_001165963.4	P4
SCN1A-AS1	ENST00000651574.1	n.488-13355T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31377 AN: 151988 Hom.: 3494 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.206 AC: 31389 AN: 152106 Hom.: 3495 Cov.: 33 AF XY: 0.211 AC XY: 15683 AN XY: 74366

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.181

Alfa AF: 0.212 Hom.: 435

Bravo AF: 0.201

Asia WGS AF: 0.296 AC: 1030 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.48

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: rs2892992; hg19: chr2-166918443;