Genetic Variant NM_181703.4:c.*508G>A (chr1-147757654-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_181703.4(GJA5):c.*508G>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 0.000467 in 152,192 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GJA5
NM_181703.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.611

Publications

0 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
congenital heart disease
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BS2

High AC in GnomAd4 at 71 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181703.4. 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
	GJA5	NM_181703.4	MANE Select	c.*508G>A		3_prime_UTR	Exon 2 of 2	NP_859054.1	P36382
	GJA5	NM_005266.7		c.*508G>A		3_prime_UTR	Exon 2 of 2	NP_005257.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GJA5	ENST00000579774.3	TSL:1 MANE Select	c.*508G>A	3_prime_UTR	Exon 2 of 2	ENSP00000463851.1	P36382
GJA5	ENST00000621517.1	TSL:2	c.*508G>A	3_prime_UTR	Exon 2 of 2	ENSP00000484552.1	P36382
GJA5	ENST00000863529.1		c.*508G>A	3_prime_UTR	Exon 2 of 2	ENSP00000533588.1

Frequencies

GnomAD3 genomes

AF:

0.000467

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

16794

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

8830

African (AFR)

AF:

0.00

AC:

AN:

202

American (AMR)

AF:

0.00

AC:

AN:

3172

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

190

East Asian (EAS)

AF:

0.00

AC:

AN:

1380

South Asian (SAS)

AF:

0.00

AC:

AN:

2330

European-Finnish (FIN)

AF:

0.00

AC:

AN:

280

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

8570

Other (OTH)

AF:

0.00

AC:

AN:

642

GnomAD4 genome

AF:

0.000467

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.00157

AC:

AN:

41524

American (AMR)

AF:

0.000393

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000442

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Atrial fibrillation, familial, 11 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.6

(source)

DANN

Benign

0.35

PhyloP100

-0.61

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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