rs2395721

Positions:

• chr6-39302702-A-C
• chr6-39302702-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.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

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=-0.83).
• 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/exons	MANE	Protein	UniProt
KCNK17	NM_031460.4	c.688+1255T>G		intron_variant		ENST00000373231.9	NP_113648.2
KCNK17	NM_001135111.2	c.688+1255T>G		intron_variant			NP_001128583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK17	ENST00000373231.9	c.688+1255T>G		intron_variant		1	NM_031460.4	ENSP00000362328	P1
KCNK17	ENST00000453413.2	c.688+1255T>G		intron_variant		5		ENSP00000401271

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

Gnomad4 AFR AF: 0.0476

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.201

Alfa AF: 0.195 Hom.: 1066

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

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: rs2395721; hg19: chr6-39270478;