rs580041

Variant names:

• chr2-166094000-C-T
• rs580041
• NM_001165963.4:c.-141-16199G>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.-141-16199G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 151,840 control chromosomes in the GnomAD database, including 5,079 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 (5079 hom., cov: 32)
• Consequence: SCN1A NM_001165963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN1A	NM_001165963.4	c.-141-16199G>A		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.-141-16199G>A		intron_variant	Intron 2 of 28		NM_001165963.4	ENSP00000501589.1
SCN1A	ENST00000303395.9	c.-141-16199G>A		intron_variant	Intron 1 of 27	5		ENSP00000303540.4
SCN1A	ENST00000409050.2	c.-187-16153G>A		intron_variant	Intron 1 of 27	5		ENSP00000386312.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38934 AN: 151722 Hom.: 5076 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.257 AC: 38953 AN: 151840 Hom.: 5079 Cov.: 32 AF XY: 0.252 AC XY: 18676 AN XY: 74226

African (AFR) AF: 0.257 AC: 10615 AN: 41356

American (AMR) AF: 0.223 AC: 3403 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1152 AN: 3464

East Asian (EAS) AF: 0.205 AC: 1060 AN: 5162

South Asian (SAS) AF: 0.176 AC: 852 AN: 4830

European-Finnish (FIN) AF: 0.251 AC: 2653 AN: 10560

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18402 AN: 67928

Other (OTH) AF: 0.275 AC: 580 AN: 2106

Alfa AF: 0.262 Hom.: 22460

Bravo AF: 0.255

Asia WGS AF: 0.216 AC: 750 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.69
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs580041; hg19: chr2-166950510;