Genetic Variant GJA5:c.*53G>A (chr1-147758109-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_181703.4(GJA5):c.*53G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,231,232 control chromosomes in the GnomAD database, including 26,000 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 0.18 ( 2593 hom., cov: 32)

Exomes 𝑓: 0.20 ( 23407 hom. )

Consequence

GJA5
NM_181703.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.559

Publications

11 publications found

Variant links:

Genes affected

GJA5 (HGNC:4279): (gap junction protein alpha 5) This gene is 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 may be associated with atrial fibrillation. Alternatively spliced transcript variants encoding the same isoform have been described. [provided by RefSeq, Jul 2008]

GJA5 Gene-Disease associations (from GenCC):

atrial fibrillation, familial, 11
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
familial atrial fibrillation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
heart conduction disease
Inheritance: AD Classification: LIMITED Submitted by: Genomics England PanelApp

GJA5 links:

ENSG00000274415 (HGNC:):

ENSG00000274415 links:

Genome browser will be placed here

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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GJA5	NM_181703.4 link	c.*53G>A	3_prime_UTR_variant	Exon 2 of 2	ENST00000579774.3	NP_859054.1	P36382X5D2H9
GJA5	NM_005266.7 link	c.*53G>A	3_prime_UTR_variant	Exon 2 of 2		NP_005257.2	P36382X5D2H9
LOC102723321	XR_922079.4 link	n.82-19452C>T	intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GJA5	ENST00000579774.3 link	c.*53G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_181703.4	ENSP00000463851.1		P36382

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26955

AN:

151984

Hom.:

2590

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.347

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.0903

Gnomad SAS

AF:

0.0678

Gnomad FIN

AF:

0.212

Gnomad MID

AF:

0.0732

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.179

GnomAD4 exome

AF:

0.199

AC:

214916

AN:

1079130

Hom.:

23407

Cov.:

AF XY:

0.195

AC XY:

107981

AN XY:

554456

show subpopulations

African (AFR)

AF:

0.112

AC:

2926

AN:

26214

American (AMR)

AF:

0.132

AC:

5841

AN:

44266

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

3553

AN:

23728

East Asian (EAS)

AF:

0.0697

AC:

2646

AN:

37954

South Asian (SAS)

AF:

0.0734

AC:

5762

AN:

78450

European-Finnish (FIN)

AF:

0.215

AC:

11339

AN:

52766

Middle Eastern (MID)

AF:

0.105

AC:

529

AN:

5060

European-Non Finnish (NFE)

AF:

0.227

AC:

173510

AN:

763048

Other (OTH)

AF:

0.185

AC:

8810

AN:

47644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

9460

18921

28381

37842

47302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4740

9480

14220

18960

23700

<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:

0.177

AC:

26971

AN:

152102

Hom.:

2593

Cov.:

AF XY:

0.172

AC XY:

12788

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.122

AC:

5055

AN:

41510

American (AMR)

AF:

0.153

AC:

2340

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

468

AN:

3470

East Asian (EAS)

AF:

0.0900

AC:

464

AN:

5158

South Asian (SAS)

AF:

0.0684

AC:

330

AN:

4822

European-Finnish (FIN)

AF:

0.212

AC:

2244

AN:

10566

Middle Eastern (MID)

AF:

0.0788

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.226

AC:

15357

AN:

67982

Other (OTH)

AF:

0.178

AC:

374

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1110

2221

3331

4442

5552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<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:

0.201

Hom.:

714

Bravo

AF:

0.172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.3

(source)

PhyloP100

-0.56

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over