ClinVar Miner

Submissions for variant NM_000088.4(COL1A1):c.4005+5G>A

gnomAD frequency: 0.00006  dbSNP: rs778417218
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000513599 SCV000608826 uncertain significance not provided 2017-06-01 criteria provided, single submitter clinical testing
Invitae RCV000631475 SCV000752556 uncertain significance Osteogenesis imperfecta type I 2024-01-01 criteria provided, single submitter clinical testing This sequence change falls in intron 49 of the COL1A1 gene. It does not directly change the encoded amino acid sequence of the COL1A1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs778417218, gnomAD 0.01%). This variant has been observed in individual(s) with COL1A1-related conditions (PMID: 25963598). ClinVar contains an entry for this variant (Variation ID: 444409). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001001319 SCV001158506 uncertain significance not specified 2019-06-27 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000513599 SCV002541425 uncertain significance not provided 2021-05-13 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002279299 SCV002565529 uncertain significance Ehlers-Danlos syndrome 2021-05-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV002376949 SCV002624524 uncertain significance Cardiovascular phenotype 2019-03-27 criteria provided, single submitter clinical testing The c.4005+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 49 in the COL1A1 gene. This alteration has been reported in an osteogenesis imperfecta cohort (Schleit J et al. Hum. Mutat., 2015 Jul;36:728-39). This nucleotide position is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002496974 SCV002777706 uncertain significance Osteogenesis imperfecta with normal sclerae, dominant form; Osteogenesis imperfecta, perinatal lethal; Osteogenesis imperfecta type III; Infantile cortical hyperostosis; Ehlers-Danlos syndrome, arthrochalasia type; Osteogenesis imperfecta type I; Osteoporosis; Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 2022-02-23 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000513599 SCV004235392 uncertain significance not provided 2023-04-21 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.