NM_080671.4:c.*302T>C

Variant names:

• chr2-223053645-T-C
• rs3795884
• NM_080671.4:c.*302T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.83).
• 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.*302T>C		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.*302T>C		3_prime_UTR	Exon 2 of 2	ENSP00000281830.5	Q8WWG9-3
	KCNE4	ENST00000488477.2	TSL:3	n.75+1371T>C		intron	N/A

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

African (AFR) AF: 0.932 AC: 8049 AN: 8640

American (AMR) AF: 0.942 AC: 12139 AN: 12888

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 6643 AN: 8092

East Asian (EAS) AF: 0.987 AC: 16203 AN: 16418

South Asian (SAS) AF: 0.922 AC: 29256 AN: 31716

European-Finnish (FIN) AF: 0.965 AC: 26218 AN: 27174

Middle Eastern (MID) AF: 0.790 AC: 896 AN: 1134

European-Non Finnish (NFE) AF: 0.936 AC: 142894 AN: 152660

Other (OTH) AF: 0.919 AC: 13994 AN: 15230

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

African (AFR) AF: 0.933 AC: 38772 AN: 41568

American (AMR) AF: 0.941 AC: 14400 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 2889 AN: 3470

East Asian (EAS) AF: 0.991 AC: 5109 AN: 5156

South Asian (SAS) AF: 0.928 AC: 4479 AN: 4824

European-Finnish (FIN) AF: 0.969 AC: 10294 AN: 10624

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.939 AC: 63870 AN: 68016

Other (OTH) AF: 0.917 AC: 1940 AN: 2116

Alfa AF: 0.930 Hom.: 84097

Bravo AF: 0.936

Asia WGS AF: 0.946 AC: 3292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.5
DANN	Benign	0.48
PhyloP100		0.17
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: rs3795884; hg19: chr2-223918363;