Variant rs1764389 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002060.3(GJA4):c.132G>A(p.Val44=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,613,864 control chromosomes in the GnomAD database, including 38,345 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 0.26 ( 6388 hom., cov: 32)

Exomes 𝑓: 0.20 ( 31957 hom. )

Consequence

GJA4
NM_002060.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0420

Variant links:

Genes affected

GJA4 (HGNC:4278): (gap junction protein alpha 4) This gene encodes a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell. Mutations in this gene have been associated with atherosclerosis and a higher risk of myocardial infarction. [provided by RefSeq, Jul 2008]

GJA4 links:

SMIM12 (HGNC:25154): (small integral membrane protein 12) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMIM12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP7

Synonymous conserved (PhyloP=-0.042 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GJA4	NM_002060.3 linkuse as main transcript	c.132G>A	p.Val44=	synonymous_variant	2/2	ENST00000342280.5
GJA4	XM_005270750.3 linkuse as main transcript	c.132G>A	p.Val44=	synonymous_variant	2/2
GJA4	XM_017001043.3 linkuse as main transcript	c.132G>A	p.Val44=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GJA4	ENST00000342280.5 linkuse as main transcript	c.132G>A	p.Val44=	synonymous_variant	2/2	1	NM_002060.3	P1
SMIM12	ENST00000426886.1 linkuse as main transcript	c.207+61426C>T		intron_variant, NMD_transcript_variant		1
GJA4	ENST00000450137.1 linkuse as main transcript	c.132G>A	p.Val44=	synonymous_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40280

AN:

152026

Hom.:

6376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.440

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.0942

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.229

GnomAD3 exomes

AF:

0.198

AC:

49845

AN:

251432

Hom.:

5970

AF XY:

0.192

AC XY:

26129

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.441

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.186

Gnomad EAS exome

AF:

0.147

Gnomad SAS exome

AF:

0.0938

Gnomad FIN exome

AF:

0.308

Gnomad NFE exome

AF:

0.209

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.201

AC:

294275

AN:

1461720

Hom.:

31957

Cov.:

AF XY:

0.198

AC XY:

143979

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.444

Gnomad4 AMR exome

AF:

0.112

Gnomad4 ASJ exome

AF:

0.185

Gnomad4 EAS exome

AF:

0.131

Gnomad4 SAS exome

AF:

0.0955

Gnomad4 FIN exome

AF:

0.310

Gnomad4 NFE exome

AF:

0.203

Gnomad4 OTH exome

AF:

0.202

GnomAD4 genome

AF:

0.265

AC:

40316

AN:

152144

Hom.:

6388

Cov.:

AF XY:

0.263

AC XY:

19586

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.440

Gnomad4 AMR

AF:

0.160

Gnomad4 ASJ

AF:

0.190

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.0932

Gnomad4 FIN

AF:

0.305

Gnomad4 NFE

AF:

0.204

Gnomad4 OTH

AF:

0.226

Alfa

AF:

0.230

Hom.:

2508

Bravo

AF:

0.264

Asia WGS

AF:

0.136

AC:

471

AN:

3478

EpiCase

AF:

0.205

EpiControl

AF:

0.205

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

9.0

DANN

Benign

0.83

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