1-147773279-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005266.7(GJA5):c.-61A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,214 control chromosomes in the GnomAD database, including 3,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3160 hom., cov: 31)

Exomes 𝑓: 0.24 ( 8 hom. )

Consequence

GJA5
NM_005266.7 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.55

Publications

18 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:

ENSG00000294222 (HGNC:):

ENSG00000294222 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

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

BP6

Variant 1-147773279-T-C is Benign according to our data. Variant chr1-147773279-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 292456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GJA5	NM_005266.7 link	c.-61A>G		5_prime_UTR_variant	Exon 1 of 2		NP_005257.2	P36382X5D2H9
LOC102723321	XR_922079.4 link	n.82-4282T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
GJA5	ENST00000621517.1 link	c.-61A>G	5_prime_UTR_variant	Exon 1 of 2	2	ENSP00000484552.1	P36382
GJA5	ENST00000430508.1 link	c.-61A>G	5_prime_UTR_variant	Exon 1 of 2	2	ENSP00000407645.1	A0A0B4J1Y3
ENSG00000294222	ENST00000721952.1 link	n.386+7388A>G	intron_variant	Intron 1 of 2
ENSG00000294222	ENST00000721953.1 link	n.388+7388A>G	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28368

AN:

151898

Hom.:

3158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0588

Gnomad AMI

AF:

0.319

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.236

Gnomad OTH

AF:

0.205

GnomAD4 exome

AF:

0.240

AC:

AN:

196

Hom.:

Cov.:

AF XY:

0.214

AC XY:

AN XY:

140

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.167

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.227

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.269

AC:

AN:

134

Other (OTH)

AF:

0.200

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.187

AC:

28394

AN:

152018

Hom.:

3160

Cov.:

AF XY:

0.186

AC XY:

13823

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.0592

AC:

2454

AN:

41484

American (AMR)

AF:

0.230

AC:

3518

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

627

AN:

3464

East Asian (EAS)

AF:

0.333

AC:

1720

AN:

5160

South Asian (SAS)

AF:

0.176

AC:

847

AN:

4806

European-Finnish (FIN)

AF:

0.230

AC:

2427

AN:

10564

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.236

AC:

16042

AN:

67958

Other (OTH)

AF:

0.206

AC:

435

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1119

2238

3357

4476

5595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<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:

0.148

Hom.:

509

Bravo

AF:

0.185

Asia WGS

AF:

0.246

AC:

854

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial atrial fibrillation

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Atrial fibrillation, familial, 11;C4551959:Atrial standstill 1

Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.56

(source)

DANN

Benign

0.43

PhyloP100

-3.5

PromoterAI

-0.058

Neutral

(source)

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over