rs12131478

Variant names:

• chr1-215013629-G-A
• rs12131478
• ENST00000391895.6:c.34+7674G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-215013629-G-A
• chr1-215013629-G-T

Variant summary

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

The ENST00000391895.6(KCNK2):​c.34+7674G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,858 control chromosomes in the GnomAD database, including 6,885 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 0.29 (6885 hom., cov: 32)
• Consequence: KCNK2 ENST00000391895.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 4 publications found

Genes affected

KCNK2 (HGNC:6277): (potassium two pore domain channel subfamily K member 2) This gene encodes one of the members of the two-pore-domain background potassium channel protein family. This type of potassium channel is formed by two homodimers that create a channel that leaks potassium out of the cell to control resting membrane potential. The channel can be opened, however, by certain anesthetics, membrane stretching, intracellular acidosis, and heat. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK2	NM_001017424.3	c.34+7674G>A		intron_variant	Intron 1 of 6		NP_001017424.1
KCNK2	XM_017001249.2	c.-85+7674G>A		intron_variant	Intron 1 of 7		XP_016856738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK2	ENST00000391895.6	c.34+7674G>A		intron_variant	Intron 1 of 6	1		ENSP00000375765.2
KCNK2	ENST00000467031.5	n.34+7674G>A		intron_variant	Intron 1 of 5	1		ENSP00000420203.1
KCNK2	ENST00000486921.5	n.34+7674G>A		intron_variant	Intron 1 of 6	5		ENSP00000418706.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44107 AN: 151740 Hom.: 6884 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.291 AC: 44129 AN: 151858 Hom.: 6885 Cov.: 32 AF XY: 0.297 AC XY: 22012 AN XY: 74172

African (AFR) AF: 0.193 AC: 7980 AN: 41410

American (AMR) AF: 0.405 AC: 6181 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1035 AN: 3470

East Asian (EAS) AF: 0.369 AC: 1906 AN: 5160

South Asian (SAS) AF: 0.540 AC: 2595 AN: 4808

European-Finnish (FIN) AF: 0.252 AC: 2648 AN: 10516

Middle Eastern (MID) AF: 0.445 AC: 129 AN: 290

European-Non Finnish (NFE) AF: 0.307 AC: 20846 AN: 67920

Other (OTH) AF: 0.309 AC: 652 AN: 2108

Alfa AF: 0.305 Hom.: 18932

Bravo AF: 0.292

Asia WGS AF: 0.434 AC: 1500 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.5
DANN	Benign	0.35
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12131478; hg19: chr1-215186972;