14-90114445-T-C

Variant names:

• chr14-90114445-T-C
• rs7143971
• NM_022054.4:c.334+51906T>C

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+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
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022054.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK13	NM_022054.4	MANE Select	c.334+51906T>C		intron	N/A	NP_071337.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK13	ENST00000282146.5	TSL:1 MANE Select	c.334+51906T>C		intron	N/A	ENSP00000282146.4

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

African (AFR) AF: 0.787 AC: 32637 AN: 41468

American (AMR) AF: 0.793 AC: 12118 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2393 AN: 3470

East Asian (EAS) AF: 0.924 AC: 4768 AN: 5162

South Asian (SAS) AF: 0.854 AC: 4117 AN: 4822

European-Finnish (FIN) AF: 0.698 AC: 7367 AN: 10552

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47149 AN: 67958

Other (OTH) AF: 0.731 AC: 1545 AN: 2114

Alfa AF: 0.710 Hom.: 103716

Bravo AF: 0.749

Asia WGS AF: 0.887 AC: 3083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.58
DANN	Benign	0.47
PhyloP100		-1.9
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: rs7143971; hg19: chr14-90580789;