rs2395721

Variant names:

• chr6-39302702-A-C
• rs2395721
• NM_031460.4:c.688+1255T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-39302702-A-C
• chr6-39302702-A-T

Variant summary

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

The NM_031460.4(KCNK17):​c.688+1255T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,164 control chromosomes in the GnomAD database, including 3,647 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 0.19 (3647 hom., cov: 32)
• Consequence: KCNK17 NM_031460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK17	NM_031460.4	c.688+1255T>G		intron_variant	Intron 4 of 4	ENST00000373231.9	NP_113648.2
KCNK17	NM_001135111.2	c.688+1255T>G		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.688+1255T>G		intron_variant	Intron 4 of 4	1	NM_031460.4	ENSP00000362328.4
KCNK17	ENST00000453413.2	c.688+1255T>G		intron_variant	Intron 4 of 5	5		ENSP00000401271.2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29477 AN: 152046 Hom.: 3642 Cov.: 32

Gnomad AFR AF: 0.0477

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.194 AC: 29494 AN: 152164 Hom.: 3647 Cov.: 32 AF XY: 0.198 AC XY: 14758 AN XY: 74394

African (AFR) AF: 0.0476 AC: 1979 AN: 41546

American (AMR) AF: 0.265 AC: 4048 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 873 AN: 3470

East Asian (EAS) AF: 0.383 AC: 1974 AN: 5158

South Asian (SAS) AF: 0.290 AC: 1396 AN: 4812

European-Finnish (FIN) AF: 0.276 AC: 2918 AN: 10588

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15652 AN: 67996

Other (OTH) AF: 0.201 AC: 424 AN: 2110

Alfa AF: 0.175 Hom.: 1705

Bravo AF: 0.190

Asia WGS AF: 0.316 AC: 1100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.13
DANN	Benign	0.77
PhyloP100		-1.0
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: rs2395721; hg19: chr6-39270478;