rs10497281

Variant names:

• chr2-166159592-A-G
• rs10497281
• ENST00000447809.2:n.260-11795A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-166159592-A-G
• chr2-166159592-A-T

Variant summary

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

The ENST00000447809.2(SCN1A-AS1):​n.260-11795A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 152,248 control chromosomes in the GnomAD database, including 646 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 0.041 (646 hom., cov: 32)
• Consequence: SCN1A-AS1 ENST00000447809.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• Publications: 1 publications found

Genes affected

SCN1A-AS1 (HGNC:54069): (SCN1A and SCN9A antisense RNA 1)

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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 6A

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Dravet syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• generalized epilepsy with febrile seizures plus

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• generalized epilepsy with febrile seizures plus, type 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: STRONG Submitted by: ClinGen
• migraine, familial hemiplegic, 3

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• arthrogryposis

  Inheritance: AD Classification: MODERATE Submitted by: Franklin by Genoox
• familial hemiplegic migraine

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• Dravet syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial or sporadic hemiplegic migraine

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Lennox-Gastaut syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• malignant migrating partial seizures of infancy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• myoclonic-astatic epilepsy

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN1A-AS1	NR_110260.1	n.260-11795A>G		intron_variant	Intron 2 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN1A-AS1	ENST00000447809.2	n.260-11795A>G		intron_variant	Intron 2 of 11	1
SCN1A-AS1	ENST00000595647.5	n.750-11795A>G		intron_variant	Intron 6 of 6	5
SCN1A-AS1	ENST00000599041.5	n.672-11795A>G		intron_variant	Intron 8 of 8	5

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6190 AN: 152128 Hom.: 643 Cov.: 32

Gnomad AFR AF: 0.00750

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.0478

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0402

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

GnomAD4 genome AF: 0.0407 AC: 6200 AN: 152248 Hom.: 646 Cov.: 32 AF XY: 0.0457 AC XY: 3403 AN XY: 74436

African (AFR) AF: 0.00748 AC: 311 AN: 41570

American (AMR) AF: 0.222 AC: 3394 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3470

East Asian (EAS) AF: 0.201 AC: 1039 AN: 5170

South Asian (SAS) AF: 0.0174 AC: 84 AN: 4818

European-Finnish (FIN) AF: 0.0478 AC: 507 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0107 AC: 725 AN: 68010

Other (OTH) AF: 0.0398 AC: 84 AN: 2112

Alfa AF: 0.0332 Hom.: 761

Bravo AF: 0.0560

Asia WGS AF: 0.111 AC: 386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.72
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10497281; hg19: chr2-167016102;