rs2099715

chr12-51800099-G-Achr12-51800099-G-T

Variant summary

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

The NM_014191.4(SCN8A):c.4795+5458G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,252 control chromosomes in the GnomAD database, including 1,135 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 0.11 (1135 hom., cov: 33)
• Consequence: SCN8A NM_014191.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226

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=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN8A	NM_001330260.2	c.4795+5458G>A		intron_variant		ENST00000627620.5
SCN8A	NM_014191.4	c.4795+5458G>A		intron_variant		ENST00000354534.11
SCN8A	NM_001177984.3	c.4672+5458G>A		intron_variant
SCN8A	NM_001369788.1	c.4672+5458G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN8A	ENST00000354534.11	c.4795+5458G>A		intron_variant		1	NM_014191.4	P4
SCN8A	ENST00000627620.5	c.4795+5458G>A		intron_variant		5	NM_001330260.2	A1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16232 AN: 152134 Hom.: 1137 Cov.: 33

Gnomad AFR AF: 0.0801

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0835

Gnomad OTH AF: 0.0955

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

GnomAD4 genome AF: 0.107 AC: 16230 AN: 152252 Hom.: 1135 Cov.: 33 AF XY: 0.115 AC XY: 8571 AN XY: 74436

Gnomad4 AFR AF: 0.0801

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.0835

Gnomad4 OTH AF: 0.0945

Alfa AF: 0.0874 Hom.: 527

Bravo AF: 0.102

Asia WGS AF: 0.257 AC: 893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	12
Dann	Benign	0.95

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: rs2099715; hg19: chr12-52193883;