rs2758912

Positions:

• chr6-39307506-A-G
• chr6-39307506-A-T

Variant summary

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

The NM_031460.4(KCNK17):​c.353-2851T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 151,966 control chromosomes in the GnomAD database, including 25,326 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 0.56 (25326 hom., cov: 32)
• Consequence: KCNK17 NM_031460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

Genes affected

KCNK17 (HGNC:14465): (potassium two pore domain channel subfamily K member 17) The protein encoded by this gene belongs to the family of potassium channel proteins containing two pore-forming P domains. This channel is an open rectifier which primarily passes outward current under physiological K+ concentrations. This gene is activated at alkaline pH. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK17	NM_031460.4	c.353-2851T>C		intron_variant		ENST00000373231.9	NP_113648.2
KCNK17	NM_001135111.2	c.353-2851T>C		intron_variant			NP_001128583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK17	ENST00000373231.9	c.353-2851T>C		intron_variant		1	NM_031460.4	ENSP00000362328	P1
KCNK17	ENST00000503878.1	n.458-2851T>C		intron_variant, non_coding_transcript_variant		1
KCNK17	ENST00000453413.2	c.353-2851T>C		intron_variant		5		ENSP00000401271

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85697 AN: 151846 Hom.: 25267 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.565 AC: 85822 AN: 151966 Hom.: 25326 Cov.: 32 AF XY: 0.565 AC XY: 41990 AN XY: 74254

Gnomad4 AFR AF: 0.743

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.540

Alfa AF: 0.485 Hom.: 37334

Bravo AF: 0.579

Asia WGS AF: 0.498 AC: 1733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.57
DANN	Benign	0.82

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: rs2758912; hg19: chr6-39275282;