rs7528988

Variant names:

• chr1-215075074-C-T
• rs7528988
• ENST00000391895.6:c.35-11294C>T

Variant summary

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

The ENST00000391895.6(KCNK2):​c.35-11294C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,046 control chromosomes in the GnomAD database, including 8,844 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 0.31 (8844 hom., cov: 33)
• Consequence: KCNK2 ENST00000391895.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000391895.6. 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_001017424.3		c.35-11294C>T		intron	N/A	NP_001017424.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK2	ENST00000391895.6	TSL:1	c.35-11294C>T		intron	N/A	ENSP00000375765.2
	KCNK2	ENST00000467031.5	TSL:1	n.35-11294C>T		intron	N/A	ENSP00000420203.1
	KCNK2	ENST00000486921.5	TSL:5	n.35-11294C>T		intron	N/A	ENSP00000418706.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47594 AN: 151928 Hom.: 8818 Cov.: 33

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.0980

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.314 AC: 47669 AN: 152046 Hom.: 8844 Cov.: 33 AF XY: 0.308 AC XY: 22927 AN XY: 74344

African (AFR) AF: 0.515 AC: 21350 AN: 41432

American (AMR) AF: 0.241 AC: 3683 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 927 AN: 3468

East Asian (EAS) AF: 0.0976 AC: 506 AN: 5184

South Asian (SAS) AF: 0.261 AC: 1259 AN: 4820

European-Finnish (FIN) AF: 0.200 AC: 2112 AN: 10572

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16793 AN: 67978

Other (OTH) AF: 0.340 AC: 717 AN: 2108

Alfa AF: 0.267 Hom.: 2559

Bravo AF: 0.324

Asia WGS AF: 0.213 AC: 741 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.36
PhyloP100		0.12
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: rs7528988; hg19: chr1-215248417;