ENST00000685980.2:n.*1607-567G>A – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000685980.2(KCNA3):n.*1607-567G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,110 control chromosomes in the GnomAD database, including 34,051 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 0.67 ( 34051 hom., cov: 33)

Consequence

KCNA3
ENST00000685980.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.256

Publications

4 publications found

Variant links:

COSMIC-nc: COSV63901962

Genes affected

KCNA3 (HGNC:6221): (potassium voltage-gated channel subfamily A member 3) Potassium 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. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. It plays an essential role in T-cell proliferation and activation. This gene appears to be intronless and it is clustered together with KCNA2 and KCNA10 genes on chromosome 1. [provided by RefSeq, Jul 2008]

KCNA3 links:

ENSG00000300042 (HGNC:):

ENSG00000300042 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000685980.2. 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
	KCNA3	NR_109845.2		n.219-567G>A		intron	N/A
	KCNA3	NR_109846.1		n.301-570G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNA3	ENST00000685980.2	n.*1607-567G>A	intron	N/A	ENSP00000513296.1	P22001-1
KCNA3	ENST00000697409.1	n.*1607-570G>A	intron	N/A	ENSP00000513297.1	P22001-1
KCNA3	ENST00000697410.1	n.*1667-567G>A	intron	N/A	ENSP00000513298.1	P22001-1

Frequencies

GnomAD3 genomes

AF:

0.669

AC:

101618

AN:

151992

Hom.:

34033

Cov.:

show subpopulations

Gnomad AFR

AF:

0.660

Gnomad AMI

AF:

0.568

Gnomad AMR

AF:

0.642

Gnomad ASJ

AF:

0.737

Gnomad EAS

AF:

0.554

Gnomad SAS

AF:

0.564

Gnomad FIN

AF:

0.664

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.694

Gnomad OTH

AF:

0.687

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.668

AC:

101678

AN:

152110

Hom.:

34051

Cov.:

AF XY:

0.662

AC XY:

49226

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.659

AC:

27354

AN:

41484

American (AMR)

AF:

0.643

AC:

9820

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.737

AC:

2558

AN:

3472

East Asian (EAS)

AF:

0.555

AC:

2869

AN:

5174

South Asian (SAS)

AF:

0.565

AC:

2727

AN:

4828

European-Finnish (FIN)

AF:

0.664

AC:

7016

AN:

10572

Middle Eastern (MID)

AF:

0.694

AC:

204

AN:

294

European-Non Finnish (NFE)

AF:

0.694

AC:

47168

AN:

67982

Other (OTH)

AF:

0.685

AC:

1444

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1752

3505

5257

7010

8762

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

818

1636

2454

3272

4090

<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:

0.689

Hom.:

53002

Bravo

AF:

0.667

Asia WGS

AF:

0.568

AC:

1976

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.8

(source)

DANN

Benign

0.70

PhyloP100

0.26

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over