rs363314

Variant names:

• chr10-117208093-T-G
• rs363314
• NM_181840.1:c.353-1404T>G

Variant summary

Our verdict is Benign. The variant received -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
• 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=-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 rank	MANE	Protein	UniProt
KCNK18	NM_181840.1	c.353-1404T>G		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.353-1404T>G		intron_variant	Intron 2 of 2	1	NM_181840.1	ENSP00000334650.1

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

African (AFR) AF: 0.340 AC: 14064 AN: 41380

American (AMR) AF: 0.515 AC: 7854 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2540 AN: 3468

East Asian (EAS) AF: 0.195 AC: 1004 AN: 5144

South Asian (SAS) AF: 0.545 AC: 2620 AN: 4808

European-Finnish (FIN) AF: 0.713 AC: 7501 AN: 10522

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45465 AN: 67938

Other (OTH) AF: 0.581 AC: 1228 AN: 2114

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
PhyloP100		-6.2
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: rs363314; hg19: chr10-118967604;