13-52714959-C-T

Variant names:

• chr13-52714959-C-T
• rs6561686
• NM_007015.3:c.469-2090G>A

Variant summary

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

The NM_007015.3(CNMD):​c.469-2090G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.957 in 152,328 control chromosomes in the GnomAD database, including 69,705 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 0.96 (69705 hom., cov: 33)
• Consequence: CNMD NM_007015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627
• Publications: 3 publications found

Genes affected

CNMD (HGNC:17005): (chondromodulin) This gene encodes a glycosylated transmembrane protein that is cleaved to form a mature, secreted protein. The N-terminus of the precursor protein shares characteristics with other surfactant proteins and is sometimes called chondrosurfactant protein although no biological activity has yet been defined for it. The C-terminus of the precursor protein contains a 25 kDa mature protein called leukocyte cell-derived chemotaxin-1 or chondromodulin-1. The mature protein promotes chondrocyte growth and inhibits angiogenesis. This gene is expressed in the avascular zone of prehypertrophic cartilage and its expression decreases during chondrocyte hypertrophy and vascular invasion. The mature protein likely plays a role in endochondral bone development by permitting cartilaginous anlagen to be vascularized and replaced by bone. It may be involved also in the broad control of tissue vascularization during development. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007015.3. 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
	CNMD	NM_007015.3	MANE Select	c.469-2090G>A		intron	N/A	NP_008946.1	O75829-1
	CNMD	NM_001011705.2		c.469-2090G>A		intron	N/A	NP_001011705.1	O75829-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNMD	ENST00000377962.8	TSL:1 MANE Select	c.469-2090G>A		intron	N/A	ENSP00000367198.3	O75829-1
	CNMD	ENST00000448904.6	TSL:1	c.469-2090G>A		intron	N/A	ENSP00000388576.2	O75829-2
	CNMD	ENST00000863287.1		c.469-2090G>A		intron	N/A	ENSP00000533346.1

Frequencies

GnomAD3 genomes AF: 0.957 AC: 145602 AN: 152210 Hom.: 69652 Cov.: 33

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.921

Gnomad FIN AF: 0.959

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.949

Gnomad OTH AF: 0.952

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

GnomAD4 genome AF: 0.957 AC: 145711 AN: 152328 Hom.: 69705 Cov.: 33 AF XY: 0.957 AC XY: 71270 AN XY: 74488

African (AFR) AF: 0.967 AC: 40191 AN: 41580

American (AMR) AF: 0.967 AC: 14790 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3257 AN: 3472

East Asian (EAS) AF: 0.992 AC: 5140 AN: 5184

South Asian (SAS) AF: 0.921 AC: 4443 AN: 4826

European-Finnish (FIN) AF: 0.959 AC: 10189 AN: 10622

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.949 AC: 64526 AN: 68024

Other (OTH) AF: 0.948 AC: 2004 AN: 2114

Alfa AF: 0.954 Hom.: 10080

Bravo AF: 0.959

Asia WGS AF: 0.945 AC: 3280 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.57
DANN	Benign	0.24
PhyloP100		-0.63
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: rs6561686; hg19: chr13-53289094;