rs11692675

Variant names:

• chr2-166069918-T-C
• rs11692675
• NM_001165963.4:c.264+3440A>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.264+3440A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,066 control chromosomes in the GnomAD database, including 6,373 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. The gene SCN1A is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: 𝑓 0.28 (6373 hom., cov: 32)
• Consequence: SCN1A NM_001165963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600
• Publications: 7 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

Specifications for SCN1A are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.333 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN1A	NM_001165963.4	MANE Select	c.264+3440A>G		intron	N/A	NP_001159435.1	P35498-1
	SCN1A	NM_001202435.3		c.264+3440A>G		intron	N/A	NP_001189364.1	P35498-1
	SCN1A	NM_001353948.2		c.264+3440A>G		intron	N/A	NP_001340877.1	P35498-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN1A	ENST00000674923.1	MANE Select	c.264+3440A>G		intron	N/A	ENSP00000501589.1	P35498-1
	SCN1A	ENST00000303395.9	TSL:5	c.264+3440A>G		intron	N/A	ENSP00000303540.4	P35498-1
	SCN1A	ENST00000375405.7	TSL:5	c.264+3440A>G		intron	N/A	ENSP00000364554.3	P35498-2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42820 AN: 151950 Hom.: 6374 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.282 AC: 42828 AN: 152066 Hom.: 6373 Cov.: 32 AF XY: 0.279 AC XY: 20713 AN XY: 74308

African (AFR) AF: 0.201 AC: 8349 AN: 41492

American (AMR) AF: 0.255 AC: 3889 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1331 AN: 3466

East Asian (EAS) AF: 0.175 AC: 907 AN: 5174

South Asian (SAS) AF: 0.277 AC: 1333 AN: 4810

European-Finnish (FIN) AF: 0.293 AC: 3098 AN: 10566

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22850 AN: 67972

Other (OTH) AF: 0.316 AC: 666 AN: 2106

Alfa AF: 0.315 Hom.: 30679

Bravo AF: 0.274

Asia WGS AF: 0.227 AC: 791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.84
DANN	Benign	0.45
PhyloP100		-0.60
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: rs11692675; hg19: chr2-166926428;