rs12214600

Variant names:

• chr6-39300960-C-T
• rs12214600
• NM_031460.4:c.689-1223G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

KCNK17 Gene-Disease associations (from GenCC):

• heart conduction disease

  Inheritance: Unknown Classification: LIMITED Submitted by: Genomics England PanelApp

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 (AMR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK17	NM_031460.4	c.689-1223G>A		intron_variant	Intron 4 of 4	ENST00000373231.9	NP_113648.2
KCNK17	NM_001135111.2	c.689-437G>A		intron_variant	Intron 4 of 5		NP_001128583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK17	ENST00000373231.9	c.689-1223G>A		intron_variant	Intron 4 of 4	1	NM_031460.4	ENSP00000362328.4
KCNK17	ENST00000453413.2	c.689-437G>A		intron_variant	Intron 4 of 5	5		ENSP00000401271.2

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

African (AFR) AF: 0.0364 AC: 1512 AN: 41546

American (AMR) AF: 0.211 AC: 3224 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3470

East Asian (EAS) AF: 0.111 AC: 574 AN: 5168

South Asian (SAS) AF: 0.150 AC: 722 AN: 4814

European-Finnish (FIN) AF: 0.206 AC: 2180 AN: 10570

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12448 AN: 67990

Other (OTH) AF: 0.145 AC: 307 AN: 2110

Alfa AF: 0.174 Hom.: 1350

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
PhyloP100		-0.24
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: rs12214600; hg19: chr6-39268736;