rs7580025

Variant names:

• chr2-18084255-C-T
• rs7580025
• ENST00000465292.5:n.306-86135C>T

Variant summary

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

The ENST00000465292.5(KCNS3):​n.306-86135C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,928 control chromosomes in the GnomAD database, including 13,977 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 0.41 (13977 hom., cov: 32)
• Consequence: KCNS3 ENST00000465292.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 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.306-86135C>T		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62890 AN: 151810 Hom.: 13954 Cov.: 32

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.414 AC: 62949 AN: 151928 Hom.: 13977 Cov.: 32 AF XY: 0.407 AC XY: 30252 AN XY: 74274

African (AFR) AF: 0.565 AC: 23386 AN: 41404

American (AMR) AF: 0.337 AC: 5149 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1309 AN: 3470

East Asian (EAS) AF: 0.110 AC: 570 AN: 5166

South Asian (SAS) AF: 0.347 AC: 1670 AN: 4806

European-Finnish (FIN) AF: 0.343 AC: 3616 AN: 10550

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25901 AN: 67938

Other (OTH) AF: 0.371 AC: 779 AN: 2098

Alfa AF: 0.388 Hom.: 19639

Bravo AF: 0.420

Asia WGS AF: 0.259 AC: 902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.45
DANN	Benign	0.56
PhyloP100		-0.71

Splicing

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

Other links and lift over

dbSNP: rs7580025; hg19: chr2-18265521;