chr2-166065703-T-C

Position:

• chr2-166065703-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001165963.4(SCN1A):​c.265-7015A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 152,220 control chromosomes in the GnomAD database, including 29 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 0.016 (29 hom., cov: 32)
• Consequence: SCN1A NM_001165963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0159 (2417/152220) while in subpopulation NFE AF= 0.0261 (1775/68006). AF 95% confidence interval is 0.0251. There are 29 homozygotes in gnomad4. There are 1142 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2417 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN1A	NM_001165963.4	c.265-7015A>G		intron_variant		ENST00000674923.1	NP_001159435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN1A	ENST00000674923.1	c.265-7015A>G		intron_variant			NM_001165963.4	ENSP00000501589	P4
SCN1A-AS1	ENST00000651574.1	n.488-9585T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2422 AN: 152104 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.00483

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00685

Gnomad FIN AF: 0.00395

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0261

Gnomad OTH AF: 0.0191

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

GnomAD4 genome AF: 0.0159 AC: 2417 AN: 152220 Hom.: 29 Cov.: 32 AF XY: 0.0153 AC XY: 1142 AN XY: 74436

Gnomad4 AFR AF: 0.00481

Gnomad4 AMR AF: 0.0151

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00644

Gnomad4 FIN AF: 0.00395

Gnomad4 NFE AF: 0.0261

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0235 Hom.: 39

Bravo AF: 0.0158

Asia WGS AF: 0.00318 AC: 11 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs12151636; hg19: chr2-166922213;