14-90077459-A-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.93).
• 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

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.578

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

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: rs942188; hg19: chr14-90543803;