chr2-17979049-C-T

Variant names:

• chr2-17979049-C-T
• rs10495674
• ENST00000465292.5:n.305+61178C>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+61178C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 152,234 control chromosomes in the GnomAD database, including 658 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 0.059 (658 hom., cov: 32)
• Consequence: KCNS3 ENST00000465292.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.307 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+61178C>T		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.0587 AC: 8930 AN: 152118 Hom.: 652 Cov.: 32

Gnomad AFR AF: 0.0502

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.0519

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0584

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

GnomAD4 genome AF: 0.0588 AC: 8951 AN: 152234 Hom.: 658 Cov.: 32 AF XY: 0.0665 AC XY: 4946 AN XY: 74428

African (AFR) AF: 0.0501 AC: 2083 AN: 41562

American (AMR) AF: 0.136 AC: 2074 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0357 AC: 124 AN: 3472

East Asian (EAS) AF: 0.320 AC: 1650 AN: 5158

South Asian (SAS) AF: 0.227 AC: 1093 AN: 4814

European-Finnish (FIN) AF: 0.0519 AC: 550 AN: 10600

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0180 AC: 1226 AN: 68022

Other (OTH) AF: 0.0634 AC: 134 AN: 2112

Alfa AF: 0.0365 Hom.: 147

Bravo AF: 0.0638

Asia WGS AF: 0.273 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.88
DANN	Benign	0.46
PhyloP100		-0.42

Splicing

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

Other links and lift over

dbSNP: rs10495674; hg19: chr2-18160315;