rs17762565

Positions:

• chr14-88190477-T-G

Variant summary

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

The NM_138317.3(KCNK10):​c.868+1747A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,154 control chromosomes in the GnomAD database, including 4,697 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 0.22 (4697 hom., cov: 32)
• Consequence: KCNK10 NM_138317.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127

Genes affected

KCNK10 (HGNC:6273): (potassium two pore domain channel subfamily K member 10) 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, and is stimulated strongly by arachidonic acid and to a lesser degree by membrane stretching, intracellular acidification, and general anaesthetics. Several alternatively spliced transcript variants encoding different isoforms have been identified 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK10	NM_138317.3	c.868+1747A>C		intron_variant		ENST00000319231.10	NP_612190.1
KCNK10	NM_021161.5	c.853+1747A>C		intron_variant			NP_066984.1
KCNK10	NM_138318.3	c.868+1747A>C		intron_variant			NP_612191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK10	ENST00000319231.10	c.868+1747A>C		intron_variant		1	NM_138317.3	ENSP00000312811	P1
KCNK10	ENST00000312350.9	c.868+1747A>C		intron_variant		1		ENSP00000310568
KCNK10	ENST00000340700.9	c.853+1747A>C		intron_variant		1		ENSP00000343104

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33140 AN: 152036 Hom.: 4696 Cov.: 32

Gnomad AFR AF: 0.0637

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.0179

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.218 AC: 33134 AN: 152154 Hom.: 4697 Cov.: 32 AF XY: 0.219 AC XY: 16274 AN XY: 74374

Gnomad4 AFR AF: 0.0635

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.0182

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.210

Alfa AF: 0.258 Hom.: 911

Bravo AF: 0.202

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.58

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: rs17762565; hg19: chr14-88656821;