rs2195144

Positions:

• chr2-166053241-T-C

Variant summary

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

The NM_001165963.4(SCN1A):​c.603-298A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 612,058 control chromosomes in the GnomAD database, including 158,501 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 0.74 (41715 hom., cov: 31)
  • Exomes 𝑓: 0.71 (116786 hom.)
• Consequence: SCN1A NM_001165963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN1A	NM_001165963.4	c.603-298A>G		intron_variant		ENST00000674923.1	NP_001159435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN1A	ENST00000674923.1	c.603-298A>G		intron_variant			NM_001165963.4	ENSP00000501589	P4
SCN1A-AS1	ENST00000651574.1	n.487+17111T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.738 AC: 111892 AN: 151684 Hom.: 41670 Cov.: 31

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.682

GnomAD4 exome AF: 0.708 AC: 325926 AN: 460256 Hom.: 116786 AF XY: 0.704 AC XY: 171925 AN XY: 244362

Gnomad4 AFR exome AF: 0.821

Gnomad4 AMR exome AF: 0.775

Gnomad4 ASJ exome AF: 0.602

Gnomad4 EAS exome AF: 0.893

Gnomad4 SAS exome AF: 0.688

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.683

Gnomad4 OTH exome AF: 0.692

GnomAD4 genome AF: 0.738 AC: 111999 AN: 151802 Hom.: 41715 Cov.: 31 AF XY: 0.741 AC XY: 54984 AN XY: 74190

Gnomad4 AFR AF: 0.824

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.890

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.756

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.684

Alfa AF: 0.712 Hom.: 4829

Bravo AF: 0.741

Asia WGS AF: 0.789 AC: 2743 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.73

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: rs2195144; hg19: chr2-166909751;