rs4300189

Variant names:

• chr1-215113078-A-G
• rs4300189
• NM_001017425.3:c.358-11555A>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.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
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.781 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.358-11555A>G		intron	N/A	NP_001017425.2
	KCNK2	NM_001017424.3		c.346-11555A>G		intron	N/A	NP_001017424.1
	KCNK2	NM_014217.4		c.313-11555A>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.358-11555A>G		intron	N/A	ENSP00000394033.2
	KCNK2	ENST00000391895.6	TSL:1	c.346-11555A>G		intron	N/A	ENSP00000375765.2
	KCNK2	ENST00000391894.6	TSL:1	c.313-11555A>G		intron	N/A	ENSP00000375764.2

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

African (AFR) AF: 0.781 AC: 32410 AN: 41486

American (AMR) AF: 0.700 AC: 10676 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2387 AN: 3468

East Asian (EAS) AF: 0.673 AC: 3467 AN: 5154

South Asian (SAS) AF: 0.547 AC: 2639 AN: 4826

European-Finnish (FIN) AF: 0.860 AC: 9120 AN: 10606

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.787 AC: 53511 AN: 67994

Other (OTH) AF: 0.734 AC: 1547 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.98
DANN	Benign	0.66
PhyloP100		-0.41
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: rs4300189; hg19: chr1-215286421;