rs4300189

Positions:

• chr1-215113078-A-G

Variant summary

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

The NM_001017425.3(KCNK2):​c.358-11555A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 152,106 control chromosomes in the GnomAD database, including 45,167 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 0.77 (45167 hom., cov: 32)
• Consequence: KCNK2 NM_001017425.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.413

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK2	NM_001017425.3	c.358-11555A>G		intron_variant		ENST00000444842.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK2	ENST00000444842.7	c.358-11555A>G		intron_variant		1	NM_001017425.3

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116727 AN: 151988 Hom.: 45130 Cov.: 32

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.768 AC: 116815 AN: 152106 Hom.: 45167 Cov.: 32 AF XY: 0.763 AC XY: 56724 AN XY: 74342

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.700

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.860

Gnomad4 NFE AF: 0.787

Gnomad4 OTH AF: 0.734

Alfa AF: 0.788 Hom.: 5865

Bravo AF: 0.763

Asia WGS AF: 0.613 AC: 2135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.98
DANN	Benign	0.66

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: rs4300189; hg19: chr1-215286421;