Variant 11-30011644-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002233.4(KCNA4):c.1035C>T(p.Gly345Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,613,708 control chromosomes in the GnomAD database, including 24,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3735 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20656 hom. )

Consequence

KCNA4
NM_002233.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.72

Variant links:

Genes affected

KCNA4 (HGNC:6222): (potassium voltage-gated channel subfamily A member 4) 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 A-type potassium current class, the members of which may be important in the regulation of the fast repolarizing phase of action potentials in heart and thus may influence the duration of cardiac action potential.[provided by RefSeq, Mar 2011]

KCNA4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 11-30011644-G-A is Benign according to our data. Variant chr11-30011644-G-A is described in ClinVar as [Benign]. Clinvar id is 1174211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.72 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNA4	NM_002233.4 linkuse as main transcript	c.1035C>T	p.Gly345Gly	synonymous_variant	2/2	ENST00000328224.7	NP_002224.1	P22459

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNA4	ENST00000328224.7 linkuse as main transcript	c.1035C>T	p.Gly345Gly	synonymous_variant	2/2	1	NM_002233.4	ENSP00000328511.6		P22459

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31571

AN:

151758

Hom.:

3735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.0375

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.168

Gnomad OTH

AF:

0.185

GnomAD3 exomes

AF:

0.171

AC:

42617

AN:

249500

Hom.:

4240

AF XY:

0.168

AC XY:

22708

AN XY:

135356

show subpopulations

Gnomad AFR exome

AF:

0.303

Gnomad AMR exome

AF:

0.167

Gnomad ASJ exome

AF:

0.257

Gnomad EAS exome

AF:

0.0371

Gnomad SAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.240

Gnomad NFE exome

AF:

0.165

Gnomad OTH exome

AF:

0.168

GnomAD4 exome

AF:

0.162

AC:

237180

AN:

1461832

Hom.:

20656

Cov.:

AF XY:

0.162

AC XY:

117659

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.308

Gnomad4 AMR exome

AF:

0.167

Gnomad4 ASJ exome

AF:

0.254

Gnomad4 EAS exome

AF:

0.0284

Gnomad4 SAS exome

AF:

0.137

Gnomad4 FIN exome

AF:

0.235

Gnomad4 NFE exome

AF:

0.158

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.208

AC:

31606

AN:

151876

Hom.:

3735

Cov.:

AF XY:

0.208

AC XY:

15472

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.302

Gnomad4 AMR

AF:

0.178

Gnomad4 ASJ

AF:

0.260

Gnomad4 EAS

AF:

0.0376

Gnomad4 SAS

AF:

0.132

Gnomad4 FIN

AF:

0.253

Gnomad4 NFE

AF:

0.168

Gnomad4 OTH

AF:

0.184

Alfa

AF:

0.172

Hom.:

5399

Bravo

AF:

0.207

Asia WGS

AF:

0.0850

AC:

295

AN:

3478

EpiCase

AF:

0.167

EpiControl

AF:

0.165

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 19, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.016

DANN

Benign

0.31

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over