1-147766499-A-G

Position:

• chr1-147766499-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005266.7(GJA5):​c.-34+6753T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,980 control chromosomes in the GnomAD database, including 9,208 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 0.34 (9208 hom., cov: 31)
• Consequence: GJA5 NM_005266.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607

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]

LOC102723321 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJA5	NM_005266.7	c.-34+6753T>C		intron_variant			NP_005257.2
LOC102723321	XR_922079.4	n.82-11062A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJA5	ENST00000621517.1	c.-34+6753T>C		intron_variant		2		ENSP00000484552.1
GJA5	ENST00000430508.1	c.-34+6753T>C		intron_variant		2		ENSP00000407645.1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51220 AN: 151862 Hom.: 9202 Cov.: 31

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.337 AC: 51261 AN: 151980 Hom.: 9208 Cov.: 31 AF XY: 0.338 AC XY: 25137 AN XY: 74288

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.352

Alfa AF: 0.303 Hom.: 1846

Bravo AF: 0.326

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs791295; hg19: chr1-147238599;