2-223053094-T-C

Variant names:

• chr2-223053094-T-C
• rs10201907
• NM_080671.4:c.264T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_080671.4(KCNE4):​c.264T>C​(p.Pro88Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 1,614,012 control chromosomes in the GnomAD database, including 728,290 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 0.96 (69681 hom., cov: 32)
  • Exomes 𝑓: 0.95 (658609 hom.)
• Consequence: KCNE4 NM_080671.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494
• Publications: 15 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.494 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE4	NM_080671.4	MANE Select	c.264T>C	p.Pro88Pro	synonymous	Exon 2 of 2	NP_542402.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNE4	ENST00000281830.4	TSL:1 MANE Select	c.264T>C	p.Pro88Pro	synonymous	Exon 2 of 2	ENSP00000281830.5
	KCNE4	ENST00000488477.2	TSL:3	n.75+820T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.956 AC: 145490 AN: 152210 Hom.: 69617 Cov.: 32

Gnomad AFR AF: 0.978

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.950

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.975

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.931

GnomAD2 exomes AF: 0.948 AC: 238150 AN: 251106 AF XY: 0.946

Gnomad AFR exome AF: 0.982

Gnomad AMR exome AF: 0.959

Gnomad ASJ exome AF: 0.831

Gnomad EAS exome AF: 0.997

Gnomad FIN exome AF: 0.973

Gnomad NFE exome AF: 0.942

Gnomad OTH exome AF: 0.923

GnomAD4 exome AF: 0.949 AC: 1387030 AN: 1461684 Hom.: 658609 Cov.: 82 AF XY: 0.948 AC XY: 689140 AN XY: 727146

African (AFR) AF: 0.979 AC: 32776 AN: 33480

American (AMR) AF: 0.957 AC: 42785 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 21631 AN: 26134

East Asian (EAS) AF: 0.986 AC: 39153 AN: 39698

South Asian (SAS) AF: 0.941 AC: 81167 AN: 86258

European-Finnish (FIN) AF: 0.971 AC: 51725 AN: 53264

Middle Eastern (MID) AF: 0.821 AC: 4735 AN: 5766

European-Non Finnish (NFE) AF: 0.950 AC: 1056428 AN: 1111972

Other (OTH) AF: 0.938 AC: 56630 AN: 60390

GnomAD4 genome AF: 0.956 AC: 145613 AN: 152328 Hom.: 69681 Cov.: 32 AF XY: 0.956 AC XY: 71204 AN XY: 74484

African (AFR) AF: 0.978 AC: 40675 AN: 41572

American (AMR) AF: 0.950 AC: 14546 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2912 AN: 3472

East Asian (EAS) AF: 0.991 AC: 5119 AN: 5164

South Asian (SAS) AF: 0.946 AC: 4571 AN: 4832

European-Finnish (FIN) AF: 0.975 AC: 10361 AN: 10622

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.946 AC: 64339 AN: 68034

Other (OTH) AF: 0.932 AC: 1969 AN: 2112

Alfa AF: 0.937 Hom.: 29070

Bravo AF: 0.956

Asia WGS AF: 0.966 AC: 3361 AN: 3478

EpiCase AF: 0.924

EpiControl AF: 0.927

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.9
DANN	Benign	0.45
PhyloP100		-0.49
Mutation Taster		=99/1	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: rs10201907; hg19: chr2-223917812; COSMIC: COSV56054751;