rs6893300

Positions:

• chr5-179708814-C-A

Variant summary

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

The NM_001746.4(CANX):​c.447-164C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,992 control chromosomes in the GnomAD database, including 4,865 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 0.24 (4865 hom., cov: 32)
• Consequence: CANX NM_001746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CANX	NM_001746.4	c.447-164C>A		intron_variant		ENST00000247461.9	NP_001737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CANX	ENST00000247461.9	c.447-164C>A		intron_variant		1	NM_001746.4	ENSP00000247461	P3

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36885 AN: 151870 Hom.: 4863 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.243 AC: 36908 AN: 151992 Hom.: 4865 Cov.: 32 AF XY: 0.242 AC XY: 17946 AN XY: 74300

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.245

Alfa AF: 0.281 Hom.: 5789

Bravo AF: 0.227

Asia WGS AF: 0.159 AC: 552 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.53

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: rs6893300; hg19: chr5-179135815;