2-223053362-C-G

Variant names:

• chr2-223053362-C-G
• rs10189762
• NM_080671.4:c.*19C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080671.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE4	NM_080671.4	MANE Select	c.*19C>G		3_prime_UTR	Exon 2 of 2	NP_542402.4	Q8WWG9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE4	ENST00000281830.4	TSL:1 MANE Select	c.*19C>G		3_prime_UTR	Exon 2 of 2	ENSP00000281830.5	Q8WWG9-3
	KCNE4	ENST00000488477.2	TSL:3	n.75+1088C>G		intron	N/A

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

GnomAD2 exomes AF: 0.938 AC: 224125 AN: 238866 AF XY: 0.936

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 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

African (AFR) AF: 0.932 AC: 31141 AN: 33414

American (AMR) AF: 0.951 AC: 42003 AN: 44176

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 21389 AN: 26028

East Asian (EAS) AF: 0.985 AC: 38932 AN: 39534

South Asian (SAS) AF: 0.926 AC: 79405 AN: 85710

European-Finnish (FIN) AF: 0.966 AC: 50801 AN: 52600

Middle Eastern (MID) AF: 0.779 AC: 4492 AN: 5766

European-Non Finnish (NFE) AF: 0.943 AC: 1046988 AN: 1109894

Other (OTH) AF: 0.926 AC: 55768 AN: 60216

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

African (AFR) AF: 0.933 AC: 38753 AN: 41540

American (AMR) AF: 0.941 AC: 14403 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2887 AN: 3472

East Asian (EAS) AF: 0.991 AC: 5098 AN: 5146

South Asian (SAS) AF: 0.927 AC: 4470 AN: 4820

European-Finnish (FIN) AF: 0.969 AC: 10296 AN: 10624

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.939 AC: 63878 AN: 68014

Other (OTH) AF: 0.917 AC: 1938 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.9
DANN	Benign	0.53
PhyloP100		2.2
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: rs10189762; hg19: chr2-223918080;