12-51714914-A-G

Position:

• chr12-51714914-A-G

Variant summary

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

The NM_014191.4(SCN8A):​c.1636-6632A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,158 control chromosomes in the GnomAD database, including 46,158 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 0.76 (46158 hom., cov: 31)
• Consequence: SCN8A NM_014191.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN8A	NM_001330260.2	c.1636-6632A>G		intron_variant		ENST00000627620.5
SCN8A	NM_014191.4	c.1636-6632A>G		intron_variant		ENST00000354534.11
SCN8A	NM_001177984.3	c.1636-6632A>G		intron_variant
SCN8A	NM_001369788.1	c.1636-6632A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN8A	ENST00000354534.11	c.1636-6632A>G		intron_variant		1	NM_014191.4	P4
SCN8A	ENST00000627620.5	c.1636-6632A>G		intron_variant		5	NM_001330260.2	A1

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115388 AN: 152040 Hom.: 46143 Cov.: 31

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.759 AC: 115448 AN: 152158 Hom.: 46158 Cov.: 31 AF XY: 0.759 AC XY: 56493 AN XY: 74394

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.845

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.901

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.909

Gnomad4 NFE AF: 0.876

Gnomad4 OTH AF: 0.785

Alfa AF: 0.827 Hom.: 25957

Bravo AF: 0.749

Asia WGS AF: 0.702 AC: 2437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.84

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: rs4762004; hg19: chr12-52108698;