14-90160020-C-T

Position:

• chr14-90160020-C-T

Variant summary

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

The NM_022054.4(KCNK13):​c.335-24091C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 151,732 control chromosomes in the GnomAD database, including 38,462 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 0.70 (38462 hom., cov: 29)
• Consequence: KCNK13 NM_022054.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK13	NM_022054.4	c.335-24091C>T		intron_variant		ENST00000282146.5	NP_071337.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK13	ENST00000282146.5	c.335-24091C>T		intron_variant		1	NM_022054.4	ENSP00000282146.4

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106784 AN: 151614 Hom.: 38429 Cov.: 29

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.704 AC: 106857 AN: 151732 Hom.: 38462 Cov.: 29 AF XY: 0.706 AC XY: 52349 AN XY: 74120

Gnomad4 AFR AF: 0.533

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.762

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.718

Alfa AF: 0.721 Hom.: 8483

Bravo AF: 0.697

Asia WGS AF: 0.712 AC: 2474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.5
DANN	Benign	0.68

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: rs1953216; hg19: chr14-90626364; COSMIC: COSV56418169;