chr13-52739109-C-A
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4BP6_ModerateBP7BS1BS2
The NM_007015.3(CNMD):c.135G>T(p.Val45=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,571,620 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0072 ( 14 hom., cov: 32)
Exomes 𝑓: 0.00058 ( 2 hom. )
Consequence
CNMD
NM_007015.3 synonymous
NM_007015.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.00400
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.09).
BP6
?
Variant 13-52739109-C-A is Benign according to our data. Variant chr13-52739109-C-A is described in ClinVar as [Benign]. Clinvar id is 718599.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.004 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00721 (1097/152218) while in subpopulation AFR AF= 0.0255 (1060/41550). AF 95% confidence interval is 0.0242. There are 14 homozygotes in gnomad4. There are 500 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 14 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNMD | NM_007015.3 | c.135G>T | p.Val45= | synonymous_variant | 2/7 | ENST00000377962.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNMD | ENST00000377962.8 | c.135G>T | p.Val45= | synonymous_variant | 2/7 | 1 | NM_007015.3 | P4 | |
CNMD | ENST00000448904.6 | c.135G>T | p.Val45= | synonymous_variant | 2/7 | 1 | A1 | ||
CNMD | ENST00000431550.1 | c.-100G>T | 5_prime_UTR_variant | 1/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00722 AC: 1098AN: 152104Hom.: 14 Cov.: 32
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GnomAD3 exomes AF: 0.00152 AC: 300AN: 197018Hom.: 2 AF XY: 0.00122 AC XY: 134AN XY: 109902
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GnomAD4 exome AF: 0.000584 AC: 829AN: 1419402Hom.: 2 Cov.: 31 AF XY: 0.000520 AC XY: 367AN XY: 706244
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 22, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at