rs595652

Positions:

• chr10-35608029-G-A
• chr10-35608029-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_153368.3(GJD4):​c.516G>A​(p.Lys172Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,610,496 control chromosomes in the GnomAD database, including 45,477 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 0.19 (3370 hom., cov: 32)
  • Exomes 𝑓: 0.23 (42107 hom.)
• Consequence: GJD4 NM_153368.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79

Genes affected

GJD4 (HGNC:23296): (gap junction protein delta 4) Connexins, such as GJD4, are involved in the formation of gap junctions, intercellular conduits that directly connect the cytoplasms of contacting cells. Each gap junction channel is formed by docking of 2 hemichannels, each of which contains 6 connexin subunits (Sohl et al., 2003 [PubMed 12881038]).[supplied by OMIM, Mar 2008]

ENSG00000273312 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-2.79 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJD4	NM_153368.3	c.516G>A	p.Lys172Lys	synonymous_variant	2/2	ENST00000321660.2	NP_699199.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJD4	ENST00000321660.2	c.516G>A	p.Lys172Lys	synonymous_variant	2/2	1	NM_153368.3	ENSP00000315070.1
ENSG00000273312	ENST00000609313.1	n.125C>T		non_coding_transcript_exon_variant	1/1	6
ENSG00000273312	ENST00000635993.1	n.-7C>T		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28488 AN: 152080 Hom.: 3367 Cov.: 32

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.182

GnomAD3 exomes AF: 0.246 AC: 60544 AN: 245754 Hom.: 8267 AF XY: 0.249 AC XY: 33312 AN XY: 133678

Gnomad AFR exome AF: 0.0389

Gnomad AMR exome AF: 0.297

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.345

Gnomad SAS exome AF: 0.297

Gnomad FIN exome AF: 0.301

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.234 AC: 341746 AN: 1458300 Hom.: 42107 Cov.: 36 AF XY: 0.236 AC XY: 171444 AN XY: 725414

Gnomad4 AFR exome AF: 0.0364

Gnomad4 AMR exome AF: 0.287

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.385

Gnomad4 SAS exome AF: 0.293

Gnomad4 FIN exome AF: 0.292

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.187 AC: 28500 AN: 152196 Hom.: 3370 Cov.: 32 AF XY: 0.194 AC XY: 14456 AN XY: 74398

Gnomad4 AFR AF: 0.0466

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.182

Alfa AF: 0.179 Hom.: 1603

Bravo AF: 0.177

Asia WGS AF: 0.294 AC: 1022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.19
DANN	Benign	0.82

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: rs595652; hg19: chr10-35896957; COSMIC: COSV58701889; COSMIC: COSV58701889;