1-147766499-A-G

Variant names:

• chr1-147766499-A-G
• rs791295
• NM_005266.7:c.-34+6753T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005266.7(GJA5):​c.-34+6753T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,980 control chromosomes in the GnomAD database, including 9,208 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 0.34 (9208 hom., cov: 31)
• Consequence: GJA5 NM_005266.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.394 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJA5	NM_005266.7		c.-34+6753T>C		intron	N/A	NP_005257.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJA5	ENST00000621517.1	TSL:2	c.-34+6753T>C		intron	N/A	ENSP00000484552.1
	GJA5	ENST00000430508.1	TSL:2	c.-34+6753T>C		intron	N/A	ENSP00000407645.1
	ENSG00000294222	ENST00000721952.1		n.386+14168T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51220 AN: 151862 Hom.: 9202 Cov.: 31

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.353

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.337 AC: 51261 AN: 151980 Hom.: 9208 Cov.: 31 AF XY: 0.338 AC XY: 25137 AN XY: 74288

African (AFR) AF: 0.211 AC: 8747 AN: 41466

American (AMR) AF: 0.338 AC: 5158 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 904 AN: 3470

East Asian (EAS) AF: 0.334 AC: 1723 AN: 5154

South Asian (SAS) AF: 0.328 AC: 1573 AN: 4796

European-Finnish (FIN) AF: 0.456 AC: 4814 AN: 10552

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27045 AN: 67952

Other (OTH) AF: 0.352 AC: 743 AN: 2112

Alfa AF: 0.328 Hom.: 3339

Bravo AF: 0.326

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
PhyloP100		-0.61

Splicing

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

Other links and lift over

dbSNP: rs791295; hg19: chr1-147238599;