2-223053645-T-C

Position:

• chr2-223053645-T-C

Variant summary

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

The NM_080671.4(KCNE4):​c.*302T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.936 in 426,236 control chromosomes in the GnomAD database, including 187,123 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 0.94 (67039 hom., cov: 32)
  • Exomes 𝑓: 0.94 (120084 hom.)
• Consequence: KCNE4 NM_080671.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173

Genes affected

KCNE4 (HGNC:6244): (potassium voltage-gated channel subfamily E regulatory subunit 4) Voltage-gated potassium (Kv) 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 member of the potassium channel, voltage-gated, isk-related subfamily. This member is a type I membrane protein, and a beta subunit that assembles with a potassium channel alpha-subunit to modulate the gating kinetics and enhance stability of the multimeric complex. This gene is prominently expressed in the embryo and in adult uterus. [provided by RefSeq, Jul 2008]

KCNE4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNE4	NM_080671.4	c.*302T>C		3_prime_UTR_variant	2/2	ENST00000281830.4	NP_542402.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNE4	ENST00000281830.4	c.*302T>C		3_prime_UTR_variant	2/2	1	NM_080671.4	ENSP00000281830.5
KCNE4	ENST00000488477.2	n.75+1371T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.938 AC: 142699 AN: 152166 Hom.: 66992 Cov.: 32

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.941

Gnomad ASJ AF: 0.833

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.929

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.915

GnomAD4 exome AF: 0.936 AC: 256292 AN: 273952 Hom.: 120084 Cov.: 2 AF XY: 0.934 AC XY: 132933 AN XY: 142352

Gnomad4 AFR exome AF: 0.932

Gnomad4 AMR exome AF: 0.942

Gnomad4 ASJ exome AF: 0.821

Gnomad4 EAS exome AF: 0.987

Gnomad4 SAS exome AF: 0.922

Gnomad4 FIN exome AF: 0.965

Gnomad4 NFE exome AF: 0.936

Gnomad4 OTH exome AF: 0.919

GnomAD4 genome AF: 0.938 AC: 142803 AN: 152284 Hom.: 67039 Cov.: 32 AF XY: 0.938 AC XY: 69829 AN XY: 74450

Gnomad4 AFR AF: 0.933

Gnomad4 AMR AF: 0.941

Gnomad4 ASJ AF: 0.833

Gnomad4 EAS AF: 0.991

Gnomad4 SAS AF: 0.928

Gnomad4 FIN AF: 0.969

Gnomad4 NFE AF: 0.939

Gnomad4 OTH AF: 0.917

Alfa AF: 0.929 Hom.: 65813

Bravo AF: 0.936

Asia WGS AF: 0.946 AC: 3292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.5
DANN	Benign	0.48

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: rs3795884; hg19: chr2-223918363;