2-18053180-C-A

Position:

• chr2-18053180-C-A

Variant summary

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

The ENST00000465292.5(KCNS3):​n.306-117210C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,038 control chromosomes in the GnomAD database, including 1,974 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 0.14 (1974 hom., cov: 32)
• Consequence: KCNS3 ENST00000465292.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186

Genes affected

KCNS3 (HGNC:6302): (potassium voltage-gated channel modifier subfamily S member 3) Voltage-gated potassium channels form the largest and most diversified class of ion channels and are present in both excitable and nonexcitable cells. Their main functions are associated with the regulation of the resting membrane potential and the control of the shape and frequency of action potentials. The alpha subunits are of 2 types: those that are functional by themselves and those that are electrically silent but capable of modulating the activity of specific functional alpha subunits. The protein encoded by this gene is not functional by itself but can form heteromultimers with member 1 and with member 2 (and possibly other members) of the Shab-related subfamily of potassium voltage-gated channel proteins. This gene belongs to the S subfamily of the potassium channel family. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNS3	ENST00000465292.5	n.306-117210C>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21807 AN: 151920 Hom.: 1976 Cov.: 32

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.143 AC: 21794 AN: 152038 Hom.: 1974 Cov.: 32 AF XY: 0.145 AC XY: 10783 AN XY: 74290

Gnomad4 AFR AF: 0.0448

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.162

Alfa AF: 0.175 Hom.: 5603

Bravo AF: 0.136

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.6
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16984239; hg19: chr2-18234446;