ENST00000465292.5:n.536-2189A>G

Variant names:

• chr2-18359378-A-G
• rs7580332
• ENST00000465292.5:n.536-2189A>G

Variant summary

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

The ENST00000465292.5(KCNS3):​n.536-2189A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,090 control chromosomes in the GnomAD database, including 11,275 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 0.37 (11275 hom., cov: 32)
• Consequence: KCNS3 ENST00000465292.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189
• Publications: 9 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.424 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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNS3	ENST00000465292.5	TSL:4	n.536-2189A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57013 AN: 151972 Hom.: 11281 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.375 AC: 57006 AN: 152090 Hom.: 11275 Cov.: 32 AF XY: 0.377 AC XY: 27992 AN XY: 74330

African (AFR) AF: 0.252 AC: 10438 AN: 41500

American (AMR) AF: 0.394 AC: 6018 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1838 AN: 3470

East Asian (EAS) AF: 0.334 AC: 1729 AN: 5174

South Asian (SAS) AF: 0.338 AC: 1630 AN: 4816

European-Finnish (FIN) AF: 0.479 AC: 5061 AN: 10556

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29089 AN: 67974

Other (OTH) AF: 0.368 AC: 778 AN: 2112

Alfa AF: 0.408 Hom.: 29139

Bravo AF: 0.366

Asia WGS AF: 0.334 AC: 1160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.2
DANN	Benign	0.33
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs7580332; hg19: chr2-18540644;