chr2-18049513-A-G

Variant names:

• chr2-18049513-A-G
• rs2345089
• ENST00000465292.5:n.306-120877A>G

Variant summary

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

The ENST00000465292.5(KCNS3):​n.306-120877A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,068 control chromosomes in the GnomAD database, including 6,496 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 0.28 (6496 hom., cov: 32)
• Consequence: KCNS3 ENST00000465292.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 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.306-120877A>G		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43257 AN: 151950 Hom.: 6494 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.285 AC: 43277 AN: 152068 Hom.: 6496 Cov.: 32 AF XY: 0.288 AC XY: 21419 AN XY: 74356

African (AFR) AF: 0.208 AC: 8628 AN: 41494

American (AMR) AF: 0.322 AC: 4920 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 867 AN: 3466

East Asian (EAS) AF: 0.522 AC: 2691 AN: 5154

South Asian (SAS) AF: 0.306 AC: 1474 AN: 4814

European-Finnish (FIN) AF: 0.298 AC: 3154 AN: 10582

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20591 AN: 67960

Other (OTH) AF: 0.305 AC: 644 AN: 2110

Alfa AF: 0.295 Hom.: 11259

Bravo AF: 0.285

Asia WGS AF: 0.415 AC: 1441 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.029
DANN	Benign	0.26
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs2345089; hg19: chr2-18230779;