Variant 2-223052911-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.81C>T(p.Gly27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 1,613,866 control chromosomes in the GnomAD database, including 407,892 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 0.71 ( 38623 hom., cov: 34)

Exomes 𝑓: 0.71 ( 369269 hom. )

Consequence

KCNE4
NM_080671.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.792

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=-0.57).

BP7

Synonymous conserved (PhyloP=0.792 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.795 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.81C>T	p.Gly27=	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.81C>T	p.Gly27=	synonymous_variant	2/2	1	NM_080671.4	ENSP00000281830	P1
KCNE4	ENST00000488477.2 linkuse as main transcript	n.75+637C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.711

AC:

108083

AN:

152092

Hom.:

38596

Cov.:

show subpopulations

Gnomad AFR

AF:

0.709

Gnomad AMI

AF:

0.644

Gnomad AMR

AF:

0.723

Gnomad ASJ

AF:

0.571

Gnomad EAS

AF:

0.654

Gnomad SAS

AF:

0.818

Gnomad FIN

AF:

0.788

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.703

Gnomad OTH

AF:

0.684

GnomAD3 exomes

AF:

0.716

AC:

179684

AN:

250882

Hom.:

64797

AF XY:

0.718

AC XY:

97427

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.716

Gnomad AMR exome

AF:

0.751

Gnomad ASJ exome

AF:

0.559

Gnomad EAS exome

AF:

0.652

Gnomad SAS exome

AF:

0.797

Gnomad FIN exome

AF:

0.785

Gnomad NFE exome

AF:

0.697

Gnomad OTH exome

AF:

0.686

GnomAD4 exome

AF:

0.709

AC:

1036894

AN:

1461656

Hom.:

369269

Cov.:

AF XY:

0.711

AC XY:

517300

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.716

Gnomad4 AMR exome

AF:

0.745

Gnomad4 ASJ exome

AF:

0.558

Gnomad4 EAS exome

AF:

0.618

Gnomad4 SAS exome

AF:

0.801

Gnomad4 FIN exome

AF:

0.784

Gnomad4 NFE exome

AF:

0.705

Gnomad4 OTH exome

AF:

0.698

GnomAD4 genome

AF:

0.711

AC:

108160

AN:

152210

Hom.:

38623

Cov.:

AF XY:

0.718

AC XY:

53410

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.709

Gnomad4 AMR

AF:

0.723

Gnomad4 ASJ

AF:

0.571

Gnomad4 EAS

AF:

0.653

Gnomad4 SAS

AF:

0.816

Gnomad4 FIN

AF:

0.788

Gnomad4 NFE

AF:

0.703

Gnomad4 OTH

AF:

0.685

Alfa

AF:

0.694

Hom.:

20787

Bravo

AF:

0.700

Asia WGS

AF:

0.721

AC:

2511

AN:

3478

EpiCase

AF:

0.671

EpiControl

AF:

0.672

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

5.5

DANN

Benign

0.65

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