1-147757554-G-A

Position:

• chr1-147757554-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000579774.3(GJA5):​c.*608C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 160,052 control chromosomes in the GnomAD database, including 2,234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2113 hom., cov: 32)
  • Exomes 𝑓: 0.15 (121 hom.)
• Consequence: GJA5 ENST00000579774.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.661

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-147757554-G-A is Benign according to our data. Variant chr1-147757554-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 292441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJA5	NM_181703.4	c.*608C>T		3_prime_UTR_variant	2/2	ENST00000579774.3	NP_859054.1
LOC102723321	XR_922079.4	n.82-20007G>A		intron_variant, non_coding_transcript_variant
GJA5	NM_005266.7	c.*608C>T		3_prime_UTR_variant	2/2		NP_005257.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJA5	ENST00000579774.3	c.*608C>T		3_prime_UTR_variant	2/2	1	NM_181703.4	ENSP00000463851	P1
	ENST00000612401.1	n.308+62G>A		intron_variant, non_coding_transcript_variant		5
GJA5	ENST00000621517.1	c.*608C>T		3_prime_UTR_variant	2/2	2		ENSP00000484552	P1
	ENST00000622634.1	n.262G>A		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21719 AN: 151780 Hom.: 2113 Cov.: 32

Gnomad AFR AF: 0.0386

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.000775

Gnomad SAS AF: 0.0330

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.145 AC: 1183 AN: 8154 Hom.: 121 Cov.: 0 AF XY: 0.135 AC XY: 581 AN XY: 4294

Gnomad4 AFR exome AF: 0.0313

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0296

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.143 AC: 21715 AN: 151898 Hom.: 2113 Cov.: 32 AF XY: 0.139 AC XY: 10309 AN XY: 74288

Gnomad4 AFR AF: 0.0385

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.000777

Gnomad4 SAS AF: 0.0333

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.148

Alfa AF: 0.187 Hom.: 548

Bravo AF: 0.134

Asia WGS AF: 0.0250 AC: 87 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	-0.59
CADD	Benign	5.2
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs36005900; hg19: chr1-147229662;