1-147773393-C-T

Position:

• chr1-147773393-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The variant allele was found at a frequency of 0.187 in 152,214 control chromosomes in the GnomAD database, including 3,165 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 (3159 hom., cov: 31)
  • Exomes 𝑓: 0.17 (6 hom.)
• Consequence: intergenic_region
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.35

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.147773393C>T		intergenic_region
LOC102723321	XR_922079.4	n.82-4168C>T		intron_variant
GJA5	NM_005266.7	c.-175G>A		upstream_gene_variant			NP_005257.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJA5	ENST00000621517.1	c.-175G>A		upstream_gene_variant		2		ENSP00000484552.1
GJA5	ENST00000430508.1	c.-175G>A		upstream_gene_variant		2		ENSP00000407645.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28344 AN: 151872 Hom.: 3157 Cov.: 31

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.109

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.174 AC: 39 AN: 224 Hom.: 6 Cov.: 0 AF XY: 0.169 AC XY: 24 AN XY: 142

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.187 AC: 28369 AN: 151990 Hom.: 3159 Cov.: 31 AF XY: 0.186 AC XY: 13805 AN XY: 74296

Gnomad4 AFR AF: 0.0590

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.205

Alfa AF: 0.109 Hom.: 187

Bravo AF: 0.185

Asia WGS AF: 0.246 AC: 854 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Familial atrial fibrillation Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35594137; hg19: chr1-147245497;