rs6893300

Variant names:

• chr5-179708814-C-A
• rs6893300
• NM_001746.4:c.447-164C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363993.1(CANX):​c.609-164C>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_001363993.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363993.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CANX	NM_001746.4	MANE Select	c.447-164C>A		intron	N/A	NP_001737.1
	CANX	NM_001363993.1		c.609-164C>A		intron	N/A	NP_001350922.1
	CANX	NM_001363994.1		c.552-164C>A		intron	N/A	NP_001350923.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CANX	ENST00000247461.9	TSL:1 MANE Select	c.447-164C>A		intron	N/A	ENSP00000247461.4
	CANX	ENST00000452673.6	TSL:1	c.447-164C>A		intron	N/A	ENSP00000391646.2
	CANX	ENST00000680984.1		c.447-164C>A		intron	N/A	ENSP00000506168.1

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

African (AFR) AF: 0.163 AC: 6776 AN: 41458

American (AMR) AF: 0.185 AC: 2816 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 806 AN: 3472

East Asian (EAS) AF: 0.168 AC: 871 AN: 5190

South Asian (SAS) AF: 0.170 AC: 817 AN: 4818

European-Finnish (FIN) AF: 0.340 AC: 3590 AN: 10544

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20503 AN: 67944

Other (OTH) AF: 0.245 AC: 516 AN: 2108

Alfa AF: 0.276 Hom.: 14546

Bravo AF: 0.227

Asia WGS AF: 0.159 AC: 552 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.53
PhyloP100		-1.7
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: rs6893300; hg19: chr5-179135815;