2-18208949-C-A

Variant names:

• chr2-18208949-C-A
• rs2345518
• ENST00000465292.5:n.424+38441C>A

Variant summary

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

The ENST00000465292.5(KCNS3):​n.424+38441C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 152,302 control chromosomes in the GnomAD database, including 65,288 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 0.93 (65288 hom., cov: 33)
• Consequence: KCNS3 ENST00000465292.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.779
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.944 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.424+38441C>A		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.925 AC: 140820 AN: 152184 Hom.: 65259 Cov.: 33

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.965

Gnomad AMR AF: 0.931

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.945

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.932

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

GnomAD4 genome AF: 0.925 AC: 140902 AN: 152302 Hom.: 65288 Cov.: 33 AF XY: 0.923 AC XY: 68751 AN XY: 74474

African (AFR) AF: 0.887 AC: 36865 AN: 41546

American (AMR) AF: 0.931 AC: 14237 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 3320 AN: 3472

East Asian (EAS) AF: 0.883 AC: 4580 AN: 5188

South Asian (SAS) AF: 0.856 AC: 4126 AN: 4822

European-Finnish (FIN) AF: 0.945 AC: 10030 AN: 10618

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.950 AC: 64609 AN: 68034

Other (OTH) AF: 0.932 AC: 1973 AN: 2116

Alfa AF: 0.945 Hom.: 129848

Bravo AF: 0.924

Asia WGS AF: 0.877 AC: 3049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.61
PhyloP100		-0.78

Splicing

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

Other links and lift over

dbSNP: rs2345518; hg19: chr2-18390215;