chr1-147758109-C-T

Variant names:

• chr1-147758109-C-T
• rs1692141
• NM_181703.4:c.*53G>A

Variant summary

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

The NM_181703.4(GJA5):​c.*53G>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 0.196 in 1,231,232 control chromosomes in the GnomAD database, including 26,000 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 0.18 (2593 hom., cov: 32)
  • Exomes 𝑓: 0.20 (23407 hom.)
• Consequence: GJA5 NM_181703.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559
• Publications: 11 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

ENSG00000274415 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

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.*53G>A		3_prime_UTR	Exon 2 of 2	NP_859054.1
	GJA5	NM_005266.7		c.*53G>A		3_prime_UTR	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.*53G>A		3_prime_UTR	Exon 2 of 2	ENSP00000463851.1
	GJA5	ENST00000621517.1	TSL:2	c.*53G>A		3_prime_UTR	Exon 2 of 2	ENSP00000484552.1
	GJA5	ENST00000863529.1		c.*53G>A		3_prime_UTR	Exon 2 of 2	ENSP00000533588.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26955 AN: 151984 Hom.: 2590 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0903

Gnomad SAS AF: 0.0678

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.199 AC: 214916 AN: 1079130 Hom.: 23407 Cov.: 15 AF XY: 0.195 AC XY: 107981 AN XY: 554456

African (AFR) AF: 0.112 AC: 2926 AN: 26214

American (AMR) AF: 0.132 AC: 5841 AN: 44266

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 3553 AN: 23728

East Asian (EAS) AF: 0.0697 AC: 2646 AN: 37954

South Asian (SAS) AF: 0.0734 AC: 5762 AN: 78450

European-Finnish (FIN) AF: 0.215 AC: 11339 AN: 52766

Middle Eastern (MID) AF: 0.105 AC: 529 AN: 5060

European-Non Finnish (NFE) AF: 0.227 AC: 173510 AN: 763048

Other (OTH) AF: 0.185 AC: 8810 AN: 47644

GnomAD4 genome AF: 0.177 AC: 26971 AN: 152102 Hom.: 2593 Cov.: 32 AF XY: 0.172 AC XY: 12788 AN XY: 74350

African (AFR) AF: 0.122 AC: 5055 AN: 41510

American (AMR) AF: 0.153 AC: 2340 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3470

East Asian (EAS) AF: 0.0900 AC: 464 AN: 5158

South Asian (SAS) AF: 0.0684 AC: 330 AN: 4822

European-Finnish (FIN) AF: 0.212 AC: 2244 AN: 10566

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.226 AC: 15357 AN: 67982

Other (OTH) AF: 0.178 AC: 374 AN: 2104

Alfa AF: 0.201 Hom.: 714

Bravo AF: 0.172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.3
PhyloP100		-0.56

Splicing

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

Other links and lift over

dbSNP: rs1692141; hg19: chr1-147230217;