rs1601012

chr12-51685722-A-C

Variant summary

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

The NM_014191.4(SCN8A):c.396-646A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 151,994 control chromosomes in the GnomAD database, including 40,420 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 0.70 (40420 hom., cov: 31)
• Consequence: SCN8A NM_014191.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

Genes affected

SCN8A (HGNC:10596): (sodium voltage-gated channel alpha subunit 8) This gene encodes a member of the sodium channel alpha subunit gene family. The encoded protein forms the ion pore region of the voltage-gated sodium channel. This protein is essential for the rapid membrane depolarization that occurs during the formation of the action potential in excitable neurons. Mutations in this gene are associated with cognitive disability, pancerebellar atrophy and ataxia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN8A	NM_001330260.2	c.396-646A>C		intron_variant		ENST00000627620.5
SCN8A	NM_014191.4	c.396-646A>C		intron_variant		ENST00000354534.11
SCN8A	NM_001177984.3	c.396-646A>C		intron_variant
SCN8A	NM_001369788.1	c.396-646A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN8A	ENST00000354534.11	c.396-646A>C		intron_variant		1	NM_014191.4	P4
SCN8A	ENST00000627620.5	c.396-646A>C		intron_variant		5	NM_001330260.2	A1

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106878 AN: 151876 Hom.: 40417 Cov.: 31

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.736

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

GnomAD4 genome AF: 0.703 AC: 106910 AN: 151994 Hom.: 40420 Cov.: 31 AF XY: 0.707 AC XY: 52500 AN XY: 74290

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.717

Gnomad4 EAS AF: 0.857

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.882

Gnomad4 NFE AF: 0.827

Gnomad4 OTH AF: 0.731

Alfa AF: 0.765 Hom.: 5783

Bravo AF: 0.691

Asia WGS AF: 0.661 AC: 2295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	3.3
Dann	Benign	0.77

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: rs1601012; hg19: chr12-52079506;