rs12214600

Positions:

• chr6-39300960-C-T

Variant summary

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

The NM_031460.4(KCNK17):​c.689-1223G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,160 control chromosomes in the GnomAD database, including 1,927 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 0.14 (1927 hom., cov: 32)
• Consequence: KCNK17 NM_031460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK17	NM_031460.4	c.689-1223G>A		intron_variant		ENST00000373231.9	NP_113648.2
KCNK17	NM_001135111.2	c.689-437G>A		intron_variant			NP_001128583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK17	ENST00000373231.9	c.689-1223G>A		intron_variant		1	NM_031460.4	ENSP00000362328	P1
KCNK17	ENST00000453413.2	c.689-437G>A		intron_variant		5		ENSP00000401271

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21787 AN: 152042 Hom.: 1925 Cov.: 32

Gnomad AFR AF: 0.0365

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.143 AC: 21795 AN: 152160 Hom.: 1927 Cov.: 32 AF XY: 0.146 AC XY: 10826 AN XY: 74360

Gnomad4 AFR AF: 0.0364

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.145

Alfa AF: 0.174 Hom.: 1202

Bravo AF: 0.137

Asia WGS AF: 0.138 AC: 480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.77

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: rs12214600; hg19: chr6-39268736;