10-117203362-G-C

Variant names:

• chr10-117203362-G-C
• rs963975
• NM_181840.1:c.352+2075G>C

Variant summary

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

The NM_181840.1(KCNK18):​c.352+2075G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 151,926 control chromosomes in the GnomAD database, including 35,181 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 0.67 (35181 hom., cov: 31)
• Consequence: KCNK18 NM_181840.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.954
• Publications: 3 publications found

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]

KCNK18 Gene-Disease associations (from GenCC):

• migraine, with or without aura, susceptibility to, 13

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK18	NM_181840.1	c.352+2075G>C		intron_variant	Intron 2 of 2	ENST00000334549.1	NP_862823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK18	ENST00000334549.1	c.352+2075G>C		intron_variant	Intron 2 of 2	1	NM_181840.1	ENSP00000334650.1

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102061 AN: 151806 Hom.: 35167 Cov.: 31

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.672 AC: 102113 AN: 151926 Hom.: 35181 Cov.: 31 AF XY: 0.671 AC XY: 49826 AN XY: 74272

African (AFR) AF: 0.556 AC: 23015 AN: 41386

American (AMR) AF: 0.636 AC: 9704 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2885 AN: 3472

East Asian (EAS) AF: 0.432 AC: 2218 AN: 5138

South Asian (SAS) AF: 0.670 AC: 3217 AN: 4800

European-Finnish (FIN) AF: 0.786 AC: 8313 AN: 10572

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.743 AC: 50483 AN: 67982

Other (OTH) AF: 0.691 AC: 1455 AN: 2106

Alfa AF: 0.645 Hom.: 2090

Bravo AF: 0.653

Asia WGS AF: 0.561 AC: 1949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.38
PhyloP100		-0.95
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: rs963975; hg19: chr10-118962873;