2-17936152-C-T

Variant names:

• chr2-17936152-C-T
• rs4832526
• ENST00000465292.5:n.305+18281C>T

Variant summary

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

The ENST00000465292.5(KCNS3):​n.305+18281C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,076 control chromosomes in the GnomAD database, including 36,459 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 0.69 (36459 hom., cov: 32)
• Consequence: KCNS3 ENST00000465292.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 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.305+18281C>T		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104269 AN: 151958 Hom.: 36419 Cov.: 32

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.717

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.686 AC: 104368 AN: 152076 Hom.: 36459 Cov.: 32 AF XY: 0.694 AC XY: 51577 AN XY: 74312

African (AFR) AF: 0.723 AC: 29988 AN: 41456

American (AMR) AF: 0.772 AC: 11795 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2365 AN: 3470

East Asian (EAS) AF: 0.982 AC: 5091 AN: 5184

South Asian (SAS) AF: 0.827 AC: 3987 AN: 4820

European-Finnish (FIN) AF: 0.630 AC: 6657 AN: 10564

Middle Eastern (MID) AF: 0.733 AC: 214 AN: 292

European-Non Finnish (NFE) AF: 0.621 AC: 42227 AN: 67982

Other (OTH) AF: 0.691 AC: 1461 AN: 2114

Alfa AF: 0.648 Hom.: 3517

Bravo AF: 0.698

Asia WGS AF: 0.888 AC: 3089 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	0.51
DANN	Benign	0.54
PhyloP100		-0.48

Splicing

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

Other links and lift over

dbSNP: rs4832526; hg19: chr2-18117419;