rs363314

Positions:

• chr10-117208093-T-G

Variant summary

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

The NM_181840.1(KCNK18):​c.353-1404T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,840 control chromosomes in the GnomAD database, including 24,727 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 0.55 (24727 hom., cov: 30)
• Consequence: KCNK18 NM_181840.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.24

Genes affected

KCNK18 (HGNC:19439): (potassium two pore domain channel subfamily K member 18) Potassium channels play a role in many cellular processes including maintenance of the action potential, muscle contraction, hormone secretion, osmotic regulation, and ion flow. This gene encodes a member of the superfamily of potassium channel proteins containing two pore-forming P domains and the encoded protein functions as an outward rectifying potassium channel. A mutation in this gene has been found to be associated with migraine with aura.[provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK18	NM_181840.1	c.353-1404T>G		intron_variant		ENST00000334549.1	NP_862823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK18	ENST00000334549.1	c.353-1404T>G		intron_variant		1	NM_181840.1	ENSP00000334650	P1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82877 AN: 151722 Hom.: 24726 Cov.: 30

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.546 AC: 82896 AN: 151840 Hom.: 24727 Cov.: 30 AF XY: 0.545 AC XY: 40420 AN XY: 74192

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.581

Alfa AF: 0.593 Hom.: 5447

Bravo AF: 0.517

Asia WGS AF: 0.362 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.036
DANN	Benign	0.47

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: rs363314; hg19: chr10-118967604;