chr2-166061538-A-G

Variant names:

• chr2-166061538-A-G
• rs1461199
• NM_001165963.4:c.265-2850T>C

Variant summary

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

The NM_001165963.4(SCN1A):​c.265-2850T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,128 control chromosomes in the GnomAD database, including 3,078 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 0.20 (3078 hom., cov: 32)
• Consequence: SCN1A NM_001165963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 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.265-2850T>C		intron	N/A	NP_001159435.1
	SCN1A	NM_001202435.3		c.265-2850T>C		intron	N/A	NP_001189364.1
	SCN1A	NM_001353948.2		c.265-2850T>C		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.265-2850T>C		intron	N/A	ENSP00000501589.1
	SCN1A	ENST00000303395.9	TSL:5	c.265-2850T>C		intron	N/A	ENSP00000303540.4
	SCN1A	ENST00000375405.7	TSL:5	c.265-2850T>C		intron	N/A	ENSP00000364554.3

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29981 AN: 152012 Hom.: 3078 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.197 AC: 29986 AN: 152128 Hom.: 3078 Cov.: 32 AF XY: 0.199 AC XY: 14798 AN XY: 74356

African (AFR) AF: 0.181 AC: 7504 AN: 41522

American (AMR) AF: 0.192 AC: 2939 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3464

East Asian (EAS) AF: 0.268 AC: 1385 AN: 5174

South Asian (SAS) AF: 0.270 AC: 1302 AN: 4816

European-Finnish (FIN) AF: 0.212 AC: 2245 AN: 10584

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.198 AC: 13462 AN: 67978

Other (OTH) AF: 0.170 AC: 359 AN: 2112

Alfa AF: 0.209 Hom.: 427

Bravo AF: 0.192

Asia WGS AF: 0.258 AC: 899 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.5
DANN	Benign	0.77
PhyloP100		0.45
Mutation Taster		=97/3	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: rs1461199; hg19: chr2-166918048;