rs4900026

Positions:

• chr14-90162290-G-A
• chr14-90162290-G-C

Variant summary

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

The NM_022054.4(KCNK13):​c.335-21821G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,094 control chromosomes in the GnomAD database, including 27,827 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 0.59 (27827 hom., cov: 33)
• Consequence: KCNK13 NM_022054.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK13	NM_022054.4	c.335-21821G>A		intron_variant		ENST00000282146.5	NP_071337.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK13	ENST00000282146.5	c.335-21821G>A		intron_variant		1	NM_022054.4	ENSP00000282146.4

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89928 AN: 151976 Hom.: 27826 Cov.: 33

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.591 AC: 89960 AN: 152094 Hom.: 27827 Cov.: 33 AF XY: 0.588 AC XY: 43705 AN XY: 74358

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.607

Alfa AF: 0.675 Hom.: 51458

Bravo AF: 0.578

Asia WGS AF: 0.533 AC: 1848 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	0.21
DANN	Benign	0.59

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: rs4900026; hg19: chr14-90628634;