1-147759423-C-T

Variant names:

• chr1-147759423-C-T
• rs1692140
• NM_181703.4:c.-33-152G>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.-33-152G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 152,298 control chromosomes in the GnomAD database, including 139 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 0.029 (139 hom., cov: 32)
• Consequence: GJA5 NM_181703.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GJA5	NM_181703.4	c.-33-152G>A		intron_variant	Intron 1 of 1	ENST00000579774.3	NP_859054.1
GJA5	NM_005266.7	c.-33-152G>A		intron_variant	Intron 1 of 1		NP_005257.2
LOC102723321	XR_922079.4	n.82-18138C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GJA5	ENST00000579774.3	c.-33-152G>A		intron_variant	Intron 1 of 1	1	NM_181703.4	ENSP00000463851.1

Frequencies

GnomAD3 genomes AF: 0.0285 AC: 4341 AN: 152180 Hom.: 136 Cov.: 32

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.00968

Gnomad ASJ AF: 0.00750

Gnomad EAS AF: 0.0121

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00767

Gnomad OTH AF: 0.0253

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

GnomAD4 genome AF: 0.0286 AC: 4360 AN: 152298 Hom.: 139 Cov.: 32 AF XY: 0.0272 AC XY: 2026 AN XY: 74470

African (AFR) AF: 0.0825 AC: 3426 AN: 41550

American (AMR) AF: 0.00967 AC: 148 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00750 AC: 26 AN: 3468

East Asian (EAS) AF: 0.0122 AC: 63 AN: 5182

South Asian (SAS) AF: 0.0189 AC: 91 AN: 4824

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00767 AC: 522 AN: 68034

Other (OTH) AF: 0.0250 AC: 53 AN: 2116

Alfa AF: 0.0389 Hom.: 74

Bravo AF: 0.0309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
PhyloP100		-0.56

Splicing

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

Other links and lift over

dbSNP: rs1692140; hg19: chr1-147231531;