ClinVar Miner

Submissions for variant NM_000088.4(COL1A1):c.1200+5G>A

gnomAD frequency: 0.00005  dbSNP: rs374322003
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000686632 SCV000814158 uncertain significance Osteogenesis imperfecta type I 2023-10-22 criteria provided, single submitter clinical testing This sequence change falls in intron 18 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 (rs374322003, gnomAD 0.007%). This variant has been observed in individuals with clinical features of autosomal dominant osteogenesis imperfecta (Inviate). ClinVar contains an entry for this variant (Variation ID: 566740). 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 may disrupt the consensus splice site. 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.
GeneDx RCV001558144 SCV001780030 uncertain significance not provided 2020-10-29 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Intronic +5 splice site variant predicted to result in aberrant splicing; however, in the absence of RNA/functional studies, the actual effect of this sequence change is unknown; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 566740; Landrum et al., 2016)
Fulgent Genetics, Fulgent Genetics RCV002499220 SCV002778791 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 2021-10-15 criteria provided, single submitter clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV001558144 SCV003799142 uncertain significance not provided 2022-10-31 criteria provided, single submitter clinical testing PP3
Ambry Genetics RCV003362890 SCV004053821 uncertain significance Cardiovascular phenotype 2023-09-11 criteria provided, single submitter clinical testing The c.1200+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 18 in the COL1A1 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may result in the creation or strengthening of a novel splice donor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004547855 SCV004759741 uncertain significance COL1A1-related disorder 2024-02-23 criteria provided, single submitter clinical testing The COL1A1 c.1200+5G>A variant is predicted to interfere with splicing. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0070% of alleles in individuals of European (Non-Finnish) descent in gnomAD At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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