2-166122240-C-A

Variant names:

• chr2-166122240-C-A
• rs7587026
• NM_001165963.4:c.-142+4684G>T

Variant summary

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

The NM_001165963.4(SCN1A):​c.-142+4684G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,044 control chromosomes in the GnomAD database, including 5,330 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 0.26 (5330 hom., cov: 32)
• Consequence: SCN1A NM_001165963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56
• Publications: 22 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN1A	NM_001165963.4	c.-142+4684G>T		intron_variant	Intron 2 of 28	ENST00000674923.1	NP_001159435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN1A	ENST00000674923.1	c.-142+4684G>T		intron_variant	Intron 2 of 28		NM_001165963.4	ENSP00000501589.1
SCN1A	ENST00000303395.9	c.-142+5531G>T		intron_variant	Intron 1 of 27	5		ENSP00000303540.4
SCN1A	ENST00000409050.2	c.-188+26807G>T		intron_variant	Intron 1 of 27	5		ENSP00000386312.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39745 AN: 151926 Hom.: 5323 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.262 AC: 39779 AN: 152044 Hom.: 5330 Cov.: 32 AF XY: 0.256 AC XY: 19051 AN XY: 74318

African (AFR) AF: 0.277 AC: 11484 AN: 41440

American (AMR) AF: 0.226 AC: 3451 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1138 AN: 3466

East Asian (EAS) AF: 0.161 AC: 833 AN: 5174

South Asian (SAS) AF: 0.176 AC: 850 AN: 4824

European-Finnish (FIN) AF: 0.253 AC: 2672 AN: 10572

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18528 AN: 67992

Other (OTH) AF: 0.278 AC: 585 AN: 2104

Alfa AF: 0.264 Hom.: 18280

Bravo AF: 0.260

Asia WGS AF: 0.189 AC: 657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.018
DANN	Benign	0.51
PhyloP100		-2.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7587026; hg19: chr2-166978750;