chr1-34794345-G-A

Variant names:

• chr1-34794345-G-A
• rs1764389
• NM_002060.3:c.132G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002060.3(GJA4):​c.132G>A​(p.Val44Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,613,864 control chromosomes in the GnomAD database, including 38,345 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 0.26 (6388 hom., cov: 32)
  • Exomes 𝑓: 0.20 (31957 hom.)
• Consequence: GJA4 NM_002060.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 16 publications found

Genes affected

GJA4 (HGNC:4278): (gap junction protein alpha 4) This gene encodes 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 have been associated with atherosclerosis and a higher risk of myocardial infarction. [provided by RefSeq, Jul 2008]

SMIM12 (HGNC:25154): (small integral membrane protein 12) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-0.042 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002060.3. 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
	GJA4	NM_002060.3	MANE Select	c.132G>A	p.Val44Val	synonymous	Exon 2 of 2	NP_002051.2	P35212

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJA4	ENST00000342280.5	TSL:1 MANE Select	c.132G>A	p.Val44Val	synonymous	Exon 2 of 2	ENSP00000343676.4	P35212
	SMIM12	ENST00000426886.1	TSL:1	n.207+61426C>T		intron	N/A	ENSP00000429902.1	E5RH51
	GJA4	ENST00000868038.1		c.132G>A	p.Val44Val	synonymous	Exon 2 of 2	ENSP00000538097.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40280 AN: 152026 Hom.: 6376 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0942

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.229

GnomAD2 exomes AF: 0.198 AC: 49845 AN: 251432 AF XY: 0.192

Gnomad AFR exome AF: 0.441

Gnomad AMR exome AF: 0.105

Gnomad ASJ exome AF: 0.186

Gnomad EAS exome AF: 0.147

Gnomad FIN exome AF: 0.308

Gnomad NFE exome AF: 0.209

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.201 AC: 294275 AN: 1461720 Hom.: 31957 Cov.: 34 AF XY: 0.198 AC XY: 143979 AN XY: 727166

African (AFR) AF: 0.444 AC: 14857 AN: 33472

American (AMR) AF: 0.112 AC: 5030 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 4834 AN: 26136

East Asian (EAS) AF: 0.131 AC: 5194 AN: 39700

South Asian (SAS) AF: 0.0955 AC: 8237 AN: 86258

European-Finnish (FIN) AF: 0.310 AC: 16580 AN: 53418

Middle Eastern (MID) AF: 0.202 AC: 1165 AN: 5768

European-Non Finnish (NFE) AF: 0.203 AC: 226168 AN: 1111860

Other (OTH) AF: 0.202 AC: 12210 AN: 60384

GnomAD4 genome AF: 0.265 AC: 40316 AN: 152144 Hom.: 6388 Cov.: 32 AF XY: 0.263 AC XY: 19586 AN XY: 74372

African (AFR) AF: 0.440 AC: 18242 AN: 41488

American (AMR) AF: 0.160 AC: 2451 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 659 AN: 3472

East Asian (EAS) AF: 0.144 AC: 746 AN: 5176

South Asian (SAS) AF: 0.0932 AC: 450 AN: 4828

European-Finnish (FIN) AF: 0.305 AC: 3228 AN: 10592

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13882 AN: 67976

Other (OTH) AF: 0.226 AC: 478 AN: 2112

Alfa AF: 0.227 Hom.: 3180

Bravo AF: 0.264

Asia WGS AF: 0.136 AC: 471 AN: 3478

EpiCase AF: 0.205

EpiControl AF: 0.205

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.0
DANN	Benign	0.83
PhyloP100		-0.042
Mutation Taster		=100/0	polymorphism (auto)

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: rs1764389; hg19: chr1-35259946; COSMIC: COSV60724757;