chr2-17933286-A-G

Variant names:

• chr2-17933286-A-G
• rs1031772
• ENST00000465292.5:n.305+15415A>G

Variant summary

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

The ENST00000465292.5(KCNS3):​n.305+15415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,210 control chromosomes in the GnomAD database, including 5,038 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 0.24 (5038 hom., cov: 33)
• Consequence: KCNS3 ENST00000465292.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382
• Publications: 7 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 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.305+15415A>G		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35903 AN: 152092 Hom.: 5041 Cov.: 33

Gnomad AFR AF: 0.0823

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.236 AC: 35885 AN: 152210 Hom.: 5038 Cov.: 33 AF XY: 0.237 AC XY: 17657 AN XY: 74420

African (AFR) AF: 0.0822 AC: 3416 AN: 41556

American (AMR) AF: 0.248 AC: 3792 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1039 AN: 3472

East Asian (EAS) AF: 0.368 AC: 1906 AN: 5186

South Asian (SAS) AF: 0.213 AC: 1028 AN: 4824

European-Finnish (FIN) AF: 0.276 AC: 2926 AN: 10590

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.306 AC: 20795 AN: 67968

Other (OTH) AF: 0.246 AC: 520 AN: 2116

Alfa AF: 0.246 Hom.: 670

Bravo AF: 0.228

Asia WGS AF: 0.256 AC: 890 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.9
DANN	Benign	0.82
PhyloP100		0.38

Splicing

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

Other links and lift over

dbSNP: rs1031772; hg19: chr2-18114553;