rs1461200

Variant names:

• chr2-166061517-C-T
• rs1461200
• NM_001165963.4:c.265-2829G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001165963.4(SCN1A):​c.265-2829G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,824 control chromosomes in the GnomAD database, including 13,221 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 0.41 (13221 hom., cov: 32)
• Consequence: SCN1A NM_001165963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN1A	NM_001165963.4	c.265-2829G>A		intron_variant	Intron 4 of 28	ENST00000674923.1	NP_001159435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN1A	ENST00000674923.1	c.265-2829G>A		intron_variant	Intron 4 of 28		NM_001165963.4	ENSP00000501589.1
SCN1A	ENST00000303395.9	c.265-2829G>A		intron_variant	Intron 3 of 27	5		ENSP00000303540.4
SCN1A	ENST00000375405.7	c.265-2829G>A		intron_variant	Intron 1 of 25	5		ENSP00000364554.3
SCN1A	ENST00000409050.2	c.265-2829G>A		intron_variant	Intron 3 of 27	5		ENSP00000386312.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61759 AN: 151706 Hom.: 13202 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.407 AC: 61816 AN: 151824 Hom.: 13221 Cov.: 32 AF XY: 0.416 AC XY: 30860 AN XY: 74174

African (AFR) AF: 0.455 AC: 18825 AN: 41390

American (AMR) AF: 0.474 AC: 7242 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 817 AN: 3466

East Asian (EAS) AF: 0.708 AC: 3649 AN: 5156

South Asian (SAS) AF: 0.436 AC: 2101 AN: 4822

European-Finnish (FIN) AF: 0.458 AC: 4819 AN: 10516

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.343 AC: 23295 AN: 67892

Other (OTH) AF: 0.339 AC: 717 AN: 2112

Alfa AF: 0.384 Hom.: 1460

Bravo AF: 0.412

Asia WGS AF: 0.538 AC: 1867 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.4
DANN	Benign	0.19
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1461200; hg19: chr2-166918027;