chr1-147758109-C-C

Variant names:

• chr1-147758109-C-C
• NM_181703.4:c.

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_181703.4(GJA5):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GJA5 NM_181703.4 exon_region
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.64
• Publications: 0 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
• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000274415 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.		exon_region	Exon 2 of 2	NP_859054.1	P36382
	GJA5	NM_181703.4	MANE Select	c.		3_prime_UTR	Exon 2 of 2	NP_859054.1	P36382
	GJA5	NM_005266.7		c.		exon_region	Exon 2 of 2	NP_005257.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJA5	ENST00000579774.3	TSL:1 MANE Select	c.		exon_region	Exon 2 of 2	ENSP00000463851.1	P36382
	GJA5	ENST00000579774.3	TSL:1 MANE Select	c.		3_prime_UTR	Exon 2 of 2	ENSP00000463851.1	P36382
	GJA5	ENST00000621517.1	TSL:2	c.		exon_region	Exon 2 of 2	ENSP00000484552.1	P36382

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 16

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6

Splicing

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

Other links and lift over

hg19: chr1-147230217;