chr2-166061933-T-A

Variant names:

• chr2-166061933-T-A
• rs2892992
• NM_001165963.4:c.265-3245A>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.265-3245A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,106 control chromosomes in the GnomAD database, including 3,495 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 0.21 (3495 hom., cov: 33)
• Consequence: SCN1A NM_001165963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001165963.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN1A	NM_001165963.4	MANE Select	c.265-3245A>T		intron	N/A	NP_001159435.1
	SCN1A	NM_001202435.3		c.265-3245A>T		intron	N/A	NP_001189364.1
	SCN1A	NM_001353948.2		c.265-3245A>T		intron	N/A	NP_001340877.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN1A	ENST00000674923.1	MANE Select	c.265-3245A>T		intron	N/A	ENSP00000501589.1
	SCN1A	ENST00000303395.9	TSL:5	c.265-3245A>T		intron	N/A	ENSP00000303540.4
	SCN1A	ENST00000375405.7	TSL:5	c.265-3245A>T		intron	N/A	ENSP00000364554.3

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31377 AN: 151988 Hom.: 3494 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.206 AC: 31389 AN: 152106 Hom.: 3495 Cov.: 33 AF XY: 0.211 AC XY: 15683 AN XY: 74366

African (AFR) AF: 0.164 AC: 6798 AN: 41536

American (AMR) AF: 0.244 AC: 3734 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 572 AN: 3468

East Asian (EAS) AF: 0.365 AC: 1885 AN: 5164

South Asian (SAS) AF: 0.278 AC: 1340 AN: 4818

European-Finnish (FIN) AF: 0.237 AC: 2511 AN: 10588

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13898 AN: 67944

Other (OTH) AF: 0.181 AC: 382 AN: 2108

Alfa AF: 0.212 Hom.: 435

Bravo AF: 0.201

Asia WGS AF: 0.296 AC: 1030 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		-0.034
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: rs2892992; hg19: chr2-166918443;