1-147758109-C-T

Position:

• chr1-147758109-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000274415 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJA5	NM_181703.4	c.*53G>A		3_prime_UTR_variant	2/2	ENST00000579774.3	NP_859054.1
GJA5	NM_005266.7	c.*53G>A		3_prime_UTR_variant	2/2		NP_005257.2
LOC102723321	XR_922079.4	n.82-19452C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJA5	ENST00000579774	c.*53G>A		3_prime_UTR_variant	2/2	1	NM_181703.4	ENSP00000463851.1
GJA5	ENST00000621517	c.*53G>A		3_prime_UTR_variant	2/2	2		ENSP00000484552.1
ENSG00000274415	ENST00000612401.1	n.309-294C>T		intron_variant		5
ENSG00000274415	ENST00000622634.1	n.480-245C>T		intron_variant		5

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

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.132

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.0697

Gnomad4 SAS exome AF: 0.0734

Gnomad4 FIN exome AF: 0.215

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.185

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

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.0900

Gnomad4 SAS AF: 0.0684

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.178

Alfa AF: 0.201 Hom.: 714

Bravo AF: 0.172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1692141; hg19: chr1-147230217;