Variant chr2-223052899-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_080671.4(KCNE4):c.69C>T(p.Ser23=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,613,998 control chromosomes in the GnomAD database, including 549 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 0.036 ( 243 hom., cov: 33)

Exomes 𝑓: 0.011 ( 306 hom. )

Consequence

KCNE4
NM_080671.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.832

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP7

Synonymous conserved (PhyloP=0.832 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNE4	NM_080671.4 linkuse as main transcript	c.69C>T	p.Ser23=	synonymous_variant	2/2	ENST00000281830.4	NP_542402.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNE4	ENST00000281830.4 linkuse as main transcript	c.69C>T	p.Ser23=	synonymous_variant	2/2	1	NM_080671.4	ENSP00000281830	P1
KCNE4	ENST00000488477.2 linkuse as main transcript	n.75+625C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0357

AC:

5437

AN:

152206

Hom.:

243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0284

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.0100

Gnomad SAS

AF:

0.0308

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00579

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0194

AC:

4851

AN:

250504

Hom.:

134

AF XY:

0.0173

AC XY:

2345

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.0361

Gnomad ASJ exome

AF:

0.000697

Gnomad EAS exome

AF:

0.00941

Gnomad SAS exome

AF:

0.0307

Gnomad FIN exome

AF:

0.00365

Gnomad NFE exome

AF:

0.00525

Gnomad OTH exome

AF:

0.0142

GnomAD4 exome

AF:

0.0110

AC:

16141

AN:

1461674

Hom.:

306

Cov.:

AF XY:

0.0111

AC XY:

8049

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.0352

Gnomad4 ASJ exome

AF:

0.000804

Gnomad4 EAS exome

AF:

0.00897

Gnomad4 SAS exome

AF:

0.0291

Gnomad4 FIN exome

AF:

0.00353

Gnomad4 NFE exome

AF:

0.00642

Gnomad4 OTH exome

AF:

0.0141

GnomAD4 genome

AF:

0.0358

AC:

5448

AN:

152324

Hom.:

243

Cov.:

AF XY:

0.0344

AC XY:

2563

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.0283

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.0101

Gnomad4 SAS

AF:

0.0309

Gnomad4 FIN

AF:

0.00235

Gnomad4 NFE

AF:

0.00579

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0184

Hom.:

Bravo

AF:

0.0410

Asia WGS

AF:

0.0290

AC:

102

AN:

3478

EpiCase

AF:

0.00649

EpiControl

AF:

0.00664

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over