14-90077459-A-T

Variant names:

• chr14-90077459-A-T
• rs942188
• NM_022054.4:c.334+14920A>T

Variant summary

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

The NM_022054.4(KCNK13):​c.334+14920A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 152,048 control chromosomes in the GnomAD database, including 29,226 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 0.61 (29226 hom., cov: 32)
• Consequence: KCNK13 NM_022054.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• Publications: 1 publications found

Genes affected

KCNK13 (HGNC:6275): (potassium two pore domain channel subfamily K member 13) Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a potassium channel containing two pore-forming domains. This protein is an open channel that can be stimulated by arachidonic acid and inhibited by the anesthetic halothane. [provided by RefSeq, Jul 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK13	NM_022054.4	c.334+14920A>T		intron_variant	Intron 1 of 1	ENST00000282146.5	NP_071337.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK13	ENST00000282146.5	c.334+14920A>T		intron_variant	Intron 1 of 1	1	NM_022054.4	ENSP00000282146.4

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92855 AN: 151928 Hom.: 29201 Cov.: 32

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.611 AC: 92926 AN: 152048 Hom.: 29226 Cov.: 32 AF XY: 0.609 AC XY: 45270 AN XY: 74312

African (AFR) AF: 0.735 AC: 30486 AN: 41484

American (AMR) AF: 0.428 AC: 6533 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2020 AN: 3466

East Asian (EAS) AF: 0.394 AC: 2041 AN: 5178

South Asian (SAS) AF: 0.515 AC: 2480 AN: 4818

European-Finnish (FIN) AF: 0.661 AC: 6976 AN: 10550

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40427 AN: 67966

Other (OTH) AF: 0.578 AC: 1222 AN: 2114

Alfa AF: 0.476 Hom.: 1268

Bravo AF: 0.599

Asia WGS AF: 0.456 AC: 1588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.3
DANN	Benign	0.75
PhyloP100		-0.28
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: rs942188; hg19: chr14-90543803;