rs4075511

Variant names:

• chr2-18062268-A-C
• rs4075511
• ENST00000465292.5:n.306-108122A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-18062268-A-C
• chr2-18062268-A-G
• chr2-18062268-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000465292.5(KCNS3):​n.306-108122A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,112 control chromosomes in the GnomAD database, including 28,735 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 0.60 (28735 hom., cov: 32)
• Consequence: KCNS3 ENST00000465292.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.887
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNS3	ENST00000465292.5	n.306-108122A>C		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90684 AN: 151994 Hom.: 28672 Cov.: 32

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.597 AC: 90806 AN: 152112 Hom.: 28735 Cov.: 32 AF XY: 0.599 AC XY: 44547 AN XY: 74366

African (AFR) AF: 0.796 AC: 33059 AN: 41514

American (AMR) AF: 0.657 AC: 10039 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1802 AN: 3468

East Asian (EAS) AF: 0.664 AC: 3429 AN: 5166

South Asian (SAS) AF: 0.663 AC: 3192 AN: 4818

European-Finnish (FIN) AF: 0.438 AC: 4635 AN: 10580

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.482 AC: 32749 AN: 67962

Other (OTH) AF: 0.567 AC: 1199 AN: 2114

Alfa AF: 0.526 Hom.: 77108

Bravo AF: 0.619

Asia WGS AF: 0.687 AC: 2392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.48
PhyloP100		-0.89

Splicing

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

Other links and lift over

dbSNP: rs4075511; hg19: chr2-18243534;