rs11120499

chr1-215125465-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017425.3(KCNK2):c.475+715T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,792 control chromosomes in the GnomAD database, including 26,460 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 0.57 (26460 hom., cov: 30)
• Consequence: KCNK2 NM_001017425.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK2	NM_001017425.3	c.475+715T>G		intron_variant		ENST00000444842.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK2	ENST00000444842.7	c.475+715T>G		intron_variant		1	NM_001017425.3

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86277 AN: 151676 Hom.: 26468 Cov.: 30

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.568 AC: 86289 AN: 151792 Hom.: 26460 Cov.: 30 AF XY: 0.568 AC XY: 42120 AN XY: 74172

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.550

Alfa AF: 0.622 Hom.: 5170

Bravo AF: 0.553

Asia WGS AF: 0.485 AC: 1692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.5
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11120499; hg19: chr1-215298808;