2-166033763-T-C

Variant names:

• chr2-166033763-T-C
• rs7571204
• NM_001165963.4:c.3429+2285A>G

Variant summary

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

The NM_001165963.4(SCN1A):​c.3429+2285A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 152,054 control chromosomes in the GnomAD database, including 41,768 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 (41768 hom., cov: 32)
• Consequence: SCN1A NM_001165963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260
• Publications: 3 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)

LOC102724058 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN1A	NM_001165963.4	c.3429+2285A>G		intron_variant	Intron 19 of 28	ENST00000674923.1	NP_001159435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN1A	ENST00000674923.1	c.3429+2285A>G		intron_variant	Intron 19 of 28		NM_001165963.4	ENSP00000501589.1
SCN1A	ENST00000303395.9	c.3429+2285A>G		intron_variant	Intron 18 of 27	5		ENSP00000303540.4
SCN1A	ENST00000375405.7	c.3396+2285A>G		intron_variant	Intron 16 of 25	5		ENSP00000364554.3
SCN1A	ENST00000409050.2	c.3345+2285A>G		intron_variant	Intron 18 of 27	5		ENSP00000386312.1

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112065 AN: 151934 Hom.: 41722 Cov.: 32

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.603

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: 0.681

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

GnomAD4 genome AF: 0.738 AC: 112173 AN: 152054 Hom.: 41768 Cov.: 32 AF XY: 0.741 AC XY: 55089 AN XY: 74324

African (AFR) AF: 0.823 AC: 34158 AN: 41496

American (AMR) AF: 0.742 AC: 11327 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2090 AN: 3468

East Asian (EAS) AF: 0.890 AC: 4612 AN: 5180

South Asian (SAS) AF: 0.709 AC: 3423 AN: 4826

European-Finnish (FIN) AF: 0.756 AC: 7993 AN: 10566

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46387 AN: 67944

Other (OTH) AF: 0.683 AC: 1444 AN: 2114

Alfa AF: 0.714 Hom.: 4718

Bravo AF: 0.740

Asia WGS AF: 0.789 AC: 2727 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.65
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: rs7571204; hg19: chr2-166890273;