rs11120499

Variant names:

• chr1-215125465-T-G
• rs11120499
• NM_001017425.3:c.475+715T>G

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017425.3. 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
	KCNK2	NM_001017425.3	MANE Select	c.475+715T>G		intron	N/A	NP_001017425.2
	KCNK2	NM_001017424.3		c.463+715T>G		intron	N/A	NP_001017424.1
	KCNK2	NM_014217.4		c.430+715T>G		intron	N/A	NP_055032.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK2	ENST00000444842.7	TSL:1 MANE Select	c.475+715T>G		intron	N/A	ENSP00000394033.2
	KCNK2	ENST00000391895.6	TSL:1	c.463+715T>G		intron	N/A	ENSP00000375765.2
	KCNK2	ENST00000391894.6	TSL:1	c.430+715T>G		intron	N/A	ENSP00000375764.2

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

African (AFR) AF: 0.344 AC: 14235 AN: 41378

American (AMR) AF: 0.560 AC: 8527 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2036 AN: 3472

East Asian (EAS) AF: 0.652 AC: 3359 AN: 5148

South Asian (SAS) AF: 0.356 AC: 1709 AN: 4804

European-Finnish (FIN) AF: 0.776 AC: 8174 AN: 10534

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.679 AC: 46114 AN: 67936

Other (OTH) AF: 0.550 AC: 1156 AN: 2100

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.5
DANN	Benign	0.68
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11120499; hg19: chr1-215298808;