14-90114445-T-C

Variant summary

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

The NM_022054.4(KCNK13):c.334+51906T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 152,028 control chromosomes in the GnomAD database, including 42,256 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 0.74 (42256 hom., cov: 31)
• Consequence: KCNK13 NM_022054.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK13	NM_022054.4	c.334+51906T>C		intron_variant		ENST00000282146.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK13	ENST00000282146.5	c.334+51906T>C		intron_variant		1	NM_022054.4	P1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112795 AN: 151910 Hom.: 42199 Cov.: 31

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.743 AC: 112914 AN: 152028 Hom.: 42256 Cov.: 31 AF XY: 0.745 AC XY: 55394 AN XY: 74306

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.924

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.731

Alfa AF: 0.701 Hom.: 61740

Bravo AF: 0.749

Asia WGS AF: 0.887 AC: 3083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.58
Dann	Benign	0.47

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: rs7143971; hg19: chr14-90580789;