Genetic Variant NM_080671.4:c.*19C>G (chr2-223053362-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.24

Publications

13 publications found

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 was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNE4	NM_080671.4 link	c.*19C>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000281830.4	NP_542402.4	Q8WWG9A5H1P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNE4	ENST00000281830.4 link	c.*19C>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_080671.4	ENSP00000281830.5		Q8WWG9
KCNE4	ENST00000488477.2 link	n.75+1088C>G		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.938

AC:

142670

AN:

152124

Hom.:

66987

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.939

AC XY:

680716

AN XY:

724692

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

3979

7958

11938

15917

19896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21574

43148

64722

86296

107870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.938

AC:

142772

AN:

152240

Hom.:

67033

Cov.:

AF XY:

0.938

AC XY:

69826

AN XY:

74440

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

454

908

1363

1817

2271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.9

(source)

DANN

Benign

0.53

PhyloP100

2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over