rs7734102

Positions:

• chr5-179726796-C-T

Variant summary

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

The NM_001746.4(CANX):​c.1725+37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,428,100 control chromosomes in the GnomAD database, including 74,059 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 0.28 (6302 hom., cov: 32)
  • Exomes 𝑓: 0.32 (67757 hom.)
• Consequence: CANX NM_001746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185

Genes affected

CANX (HGNC:1473): (calnexin) This gene encodes a member of the calnexin family of molecular chaperones. The encoded protein is a calcium-binding, endoplasmic reticulum (ER)-associated protein that interacts transiently with newly synthesized N-linked glycoproteins, facilitating protein folding and assembly. It may also play a central role in the quality control of protein folding by retaining incorrectly folded protein subunits within the ER for degradation. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CANX	NM_001746.4	c.1725+37C>T		intron_variant		ENST00000247461.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CANX	ENST00000247461.9	c.1725+37C>T		intron_variant		1	NM_001746.4	P3

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42545 AN: 151824 Hom.: 6296 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.285

GnomAD3 exomes AF: 0.273 AC: 67740 AN: 247854 Hom.: 10012 AF XY: 0.274 AC XY: 36722 AN XY: 134168

Gnomad AFR exome AF: 0.212

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.272

Gnomad EAS exome AF: 0.159

Gnomad SAS exome AF: 0.189

Gnomad FIN exome AF: 0.348

Gnomad NFE exome AF: 0.331

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.320 AC: 408351 AN: 1276158 Hom.: 67757 Cov.: 18 AF XY: 0.315 AC XY: 203338 AN XY: 644514

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.201

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.349

Gnomad4 NFE exome AF: 0.347

Gnomad4 OTH exome AF: 0.306

GnomAD4 genome AF: 0.280 AC: 42581 AN: 151942 Hom.: 6302 Cov.: 32 AF XY: 0.277 AC XY: 20553 AN XY: 74230

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.282

Alfa AF: 0.314 Hom.: 10677

Bravo AF: 0.267

Asia WGS AF: 0.180 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.50
DANN	Benign	0.24

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: rs7734102; hg19: chr5-179153797; COSMIC: COSV56003372; COSMIC: COSV56003372;