chr2-18172250-T-C

Variant names:

• chr2-18172250-T-C
• rs10495680
• ENST00000465292.5:n.424+1742T>C

Variant summary

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

The ENST00000465292.5(KCNS3):​n.424+1742T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 152,246 control chromosomes in the GnomAD database, including 197 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 0.043 (197 hom., cov: 32)
• Consequence: KCNS3 ENST00000465292.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000465292.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNS3	ENST00000465292.5	TSL:4	n.424+1742T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6552 AN: 152128 Hom.: 195 Cov.: 32

Gnomad AFR AF: 0.0277

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0493

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0415

Gnomad OTH AF: 0.0421

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

GnomAD4 genome AF: 0.0432 AC: 6570 AN: 152246 Hom.: 197 Cov.: 32 AF XY: 0.0447 AC XY: 3326 AN XY: 74448

African (AFR) AF: 0.0278 AC: 1156 AN: 41542

American (AMR) AF: 0.0496 AC: 758 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3472

East Asian (EAS) AF: 0.121 AC: 628 AN: 5176

South Asian (SAS) AF: 0.138 AC: 665 AN: 4826

European-Finnish (FIN) AF: 0.0311 AC: 330 AN: 10598

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0415 AC: 2822 AN: 68020

Other (OTH) AF: 0.0408 AC: 86 AN: 2110

Alfa AF: 0.0460 Hom.: 114

Bravo AF: 0.0420

Asia WGS AF: 0.114 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.52
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs10495680; hg19: chr2-18353516;