1-147773279-T-C

Variant names:

• chr1-147773279-T-C
• rs11552588
• NM_005266.7:c.-61A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.55
• Publications: 18 publications found

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

ENSG00000294222 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005266.7. 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_005266.7		c.-61A>G		5_prime_UTR	Exon 1 of 2	NP_005257.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJA5	ENST00000621517.1	TSL:2	c.-61A>G		5_prime_UTR	Exon 1 of 2	ENSP00000484552.1
	GJA5	ENST00000863529.1		c.-58A>G		5_prime_UTR	Exon 1 of 2	ENSP00000533588.1
	GJA5	ENST00000955979.1		c.-220A>G		5_prime_UTR	Exon 1 of 3	ENSP00000626038.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28368 AN: 151898 Hom.: 3158 Cov.: 31

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: 47 AN: 196 Hom.: 8 Cov.: 0 AF XY: 0.214 AC XY: 30 AN XY: 140

African (AFR) AF: 0.167 AC: 1 AN: 6

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.167 AC: 1 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.227 AC: 5 AN: 22

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 6

European-Non Finnish (NFE) AF: 0.269 AC: 36 AN: 134

Other (OTH) AF: 0.200 AC: 4 AN: 20

GnomAD4 genome AF: 0.187 AC: 28394 AN: 152018 Hom.: 3160 Cov.: 31 AF XY: 0.186 AC XY: 13823 AN XY: 74304

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: 34 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16042 AN: 67958

Other (OTH) AF: 0.206 AC: 435 AN: 2110

Alfa AF: 0.148 Hom.: 509

Bravo AF: 0.185

Asia WGS AF: 0.246 AC: 854 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Atrial fibrillation, familial, 11;C4551959:Atrial standstill 1 (1)
-	-	1	Familial atrial fibrillation (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.56
DANN	Benign	0.43
PhyloP100		-3.5
PromoterAI		-0.058	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11552588; hg19: chr1-147245383;