2-166135289-C-T

Position:

• chr2-166135289-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001202435.3(SCN1A):​c.-142+13758G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,082 control chromosomes in the GnomAD database, including 4,523 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 0.24 (4523 hom., cov: 32)
• Consequence: SCN1A NM_001202435.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114

Genes affected

SCN1A-AS1 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN1A	NM_001202435.3	c.-142+13758G>A		intron_variant			NP_001189364.1
SCN1A	NM_001353949.2	c.-50+13758G>A		intron_variant			NP_001340878.1
SCN1A	NM_001353950.2	c.-142+13758G>A		intron_variant			NP_001340879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN1A-AS1	ENST00000447809.2	n.260-36098C>T		intron_variant		1
SCN1A	ENST00000635750.1	c.-50+13758G>A		intron_variant		5		ENSP00000490799.1
SCN1A	ENST00000641575.1	c.-188+13758G>A		intron_variant				ENSP00000492917.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36654 AN: 151964 Hom.: 4519 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.241 AC: 36681 AN: 152082 Hom.: 4523 Cov.: 32 AF XY: 0.237 AC XY: 17638 AN XY: 74328

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.260

Alfa AF: 0.251 Hom.: 600

Bravo AF: 0.237

Asia WGS AF: 0.189 AC: 656 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3919196; hg19: chr2-166991799;