2-223053362-C-G

Position:

• chr2-223053362-C-G

Variant summary

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

The NM_080671.4(KCNE4):​c.*19C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 1,609,578 control chromosomes in the GnomAD database, including 712,396 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 (67033 hom., cov: 31)
  • Exomes 𝑓: 0.94 (645363 hom.)
• Consequence: KCNE4 NM_080671.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24

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=-0.8).
• 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.*19C>G		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.*19C>G		3_prime_UTR_variant	2/2	1	NM_080671.4	ENSP00000281830.5
KCNE4	ENST00000488477.2	n.75+1088C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.938 AC: 142670 AN: 152124 Hom.: 66987 Cov.: 31

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.941

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.915

GnomAD3 exomes AF: 0.938 AC: 224125 AN: 238866 Hom.: 105314 AF XY: 0.936 AC XY: 122153 AN XY: 130556

Gnomad AFR exome AF: 0.936

Gnomad AMR exome AF: 0.953

Gnomad ASJ exome AF: 0.825

Gnomad EAS exome AF: 0.997

Gnomad SAS exome AF: 0.924

Gnomad FIN exome AF: 0.968

Gnomad NFE exome AF: 0.934

Gnomad OTH exome AF: 0.911

GnomAD4 exome AF: 0.941 AC: 1370919 AN: 1457338 Hom.: 645363 Cov.: 41 AF XY: 0.939 AC XY: 680716 AN XY: 724692

Gnomad4 AFR exome AF: 0.932

Gnomad4 AMR exome AF: 0.951

Gnomad4 ASJ exome AF: 0.822

Gnomad4 EAS exome AF: 0.985

Gnomad4 SAS exome AF: 0.926

Gnomad4 FIN exome AF: 0.966

Gnomad4 NFE exome AF: 0.943

Gnomad4 OTH exome AF: 0.926

GnomAD4 genome AF: 0.938 AC: 142772 AN: 152240 Hom.: 67033 Cov.: 31 AF XY: 0.938 AC XY: 69826 AN XY: 74440

Gnomad4 AFR AF: 0.933

Gnomad4 AMR AF: 0.941

Gnomad4 ASJ AF: 0.832

Gnomad4 EAS AF: 0.991

Gnomad4 SAS AF: 0.927

Gnomad4 FIN AF: 0.969

Gnomad4 NFE AF: 0.939

Gnomad4 OTH AF: 0.917

Alfa AF: 0.906 Hom.: 6696

Bravo AF: 0.936

Asia WGS AF: 0.947 AC: 3295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.9
DANN	Benign	0.53

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: rs10189762; hg19: chr2-223918080;