13-52714959-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNMD	NM_007015.3	c.469-2090G>A		intron_variant	Intron 4 of 6	ENST00000377962.8	NP_008946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNMD	ENST00000377962.8	c.469-2090G>A		intron_variant	Intron 4 of 6	1	NM_007015.3	ENSP00000367198.3
CNMD	ENST00000448904.6	c.469-2090G>A		intron_variant	Intron 4 of 6	1		ENSP00000388576.2
CNMD	ENST00000431550.1	c.235-2090G>A		intron_variant	Intron 3 of 3	2		ENSP00000396035.1

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

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.967

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.992

Gnomad4 SAS AF: 0.921

Gnomad4 FIN AF: 0.959

Gnomad4 NFE AF: 0.949

Gnomad4 OTH AF: 0.948

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 v4.3

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