rs72653147
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000088.4(COL1A1):c.2644C>T(p.Arg882Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R882R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000088.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL1A1 | NM_000088.4 | c.2644C>T | p.Arg882Ter | stop_gained | 38/51 | ENST00000225964.10 | |
COL1A1 | XM_011524341.2 | c.2446C>T | p.Arg816Ter | stop_gained | 35/48 | ||
COL1A1 | XM_005257058.5 | c.2644C>T | p.Arg882Ter | stop_gained | 38/49 | ||
COL1A1 | XM_005257059.5 | c.1726C>T | p.Arg576Ter | stop_gained | 25/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL1A1 | ENST00000225964.10 | c.2644C>T | p.Arg882Ter | stop_gained | 38/51 | 1 | NM_000088.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 38
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:2Other:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2023 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26627451, 31414283, 25533962, 21667357, 16786509, 22753364, 30614853, 27044453, 33939306, 33166682, 35476365, 15241796) - |
not provided, no classification provided | in vitro | Human Development and Health, University of Southampton | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 27, 2020 | - - |
Osteogenesis imperfecta Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jan 01, 2020 | - - |
Osteogenesis imperfecta type I Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 19, 2023 | This sequence change creates a premature translational stop signal (p.Arg882*) in the COL1A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL1A1 are known to be pathogenic (PMID: 7942841, 9295084, 9443882). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with osteogenesis imperfecta type I (PMID: 15241796, 21667357, 22753364, 26627451, 27044453). ClinVar contains an entry for this variant (Variation ID: 456753). For these reasons, this variant has been classified as Pathogenic. - |
Osteogenesis imperfecta;C4551623:Ehlers-Danlos syndrome, arthrochalasia type Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Pathogenic and reported on 08-03-2018 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at