rs36005900

Variant names:

• chr1-147757554-G-A
• rs36005900
• NM_181703.4:c.*608C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181703.4(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 NM_181703.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.661
• Publications: 6 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
• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000274415 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181703.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJA5	NM_181703.4	MANE Select	c.*608C>T		3_prime_UTR	Exon 2 of 2	NP_859054.1	P36382
	GJA5	NM_005266.7		c.*608C>T		3_prime_UTR	Exon 2 of 2	NP_005257.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJA5	ENST00000579774.3	TSL:1 MANE Select	c.*608C>T		3_prime_UTR	Exon 2 of 2	ENSP00000463851.1	P36382
	GJA5	ENST00000621517.1	TSL:2	c.*608C>T		3_prime_UTR	Exon 2 of 2	ENSP00000484552.1	P36382
	GJA5	ENST00000863529.1		c.*608C>T		3_prime_UTR	Exon 2 of 2	ENSP00000533588.1

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

African (AFR) AF: 0.0313 AC: 1 AN: 32

American (AMR) AF: 0.113 AC: 255 AN: 2266

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 3 AN: 26

East Asian (EAS) AF: 0.00 AC: 0 AN: 342

South Asian (SAS) AF: 0.0296 AC: 31 AN: 1048

European-Finnish (FIN) AF: 0.207 AC: 12 AN: 58

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.203 AC: 833 AN: 4102

Other (OTH) AF: 0.174 AC: 48 AN: 276

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

African (AFR) AF: 0.0385 AC: 1592 AN: 41376

American (AMR) AF: 0.130 AC: 1977 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 404 AN: 3468

East Asian (EAS) AF: 0.000777 AC: 4 AN: 5148

South Asian (SAS) AF: 0.0333 AC: 160 AN: 4810

European-Finnish (FIN) AF: 0.211 AC: 2236 AN: 10582

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14733 AN: 67952

Other (OTH) AF: 0.148 AC: 312 AN: 2110

Alfa AF: 0.193 Hom.: 1026

Bravo AF: 0.134

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Familial atrial fibrillation (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.2
DANN	Benign	0.76
PhyloP100		0.66

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

Other links and lift over

dbSNP: rs36005900; hg19: chr1-147229662;