2-18313229-G-C

Variant names:

• chr2-18313229-G-C
• rs6721414
• ENST00000465292.5:n.425-5421G>C

Variant summary

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

The ENST00000465292.5(KCNS3):​n.425-5421G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,926 control chromosomes in the GnomAD database, including 18,318 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 0.48 (18318 hom., cov: 32)
• Consequence: KCNS3 ENST00000465292.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322
• Publications: 0 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 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.425-5421G>C		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72242 AN: 151808 Hom.: 18307 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.476 AC: 72293 AN: 151926 Hom.: 18318 Cov.: 32 AF XY: 0.480 AC XY: 35673 AN XY: 74254

African (AFR) AF: 0.581 AC: 24089 AN: 41444

American (AMR) AF: 0.493 AC: 7525 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1788 AN: 3466

East Asian (EAS) AF: 0.857 AC: 4420 AN: 5156

South Asian (SAS) AF: 0.683 AC: 3292 AN: 4818

European-Finnish (FIN) AF: 0.327 AC: 3450 AN: 10544

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26134 AN: 67916

Other (OTH) AF: 0.492 AC: 1040 AN: 2114

Alfa AF: 0.266 Hom.: 593

Bravo AF: 0.487

Asia WGS AF: 0.746 AC: 2593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.91
DANN	Benign	0.34
PhyloP100		-0.32

Splicing

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

Other links and lift over

dbSNP: rs6721414; hg19: chr2-18494495;