ClinVar Miner

Submissions for variant NM_000088.3(COL1A1):c.1984-5C>A (rs66592376)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 14
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000177437 SCV000229293 benign not specified 2015-05-19 criteria provided, single submitter clinical testing
GeneDx RCV000177437 SCV000512685 benign not specified 2017-12-20 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514224 SCV000609655 likely benign not provided 2017-08-31 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000177437 SCV000612896 benign not specified 2017-07-17 criteria provided, single submitter clinical testing
Invitae RCV000989945 SCV000627192 benign Osteogenesis imperfecta type I 2020-12-03 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000659353 SCV000781164 uncertain significance Connective tissue disease 2016-11-01 criteria provided, single submitter clinical testing
Mendelics RCV000989945 SCV001140688 likely benign Osteogenesis imperfecta type I 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283439 SCV001157099 benign none provided 2019-11-08 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001125582 SCV001284667 likely benign Ehlers-Danlos syndrome, arthrochalasia type, 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV001127681 SCV001287018 uncertain significance Infantile cortical hyperostosis 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001127682 SCV001287019 uncertain significance Osteogenesis imperfecta 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000177437 SCV001467769 benign not specified 2020-12-08 criteria provided, single submitter clinical testing Variant summary: COL1A1 c.1984-5C>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.003 in 244168 control chromosomes, predominantly at a frequency of 0.0051 within the Non-Finnish European subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 180 fold of the estimated maximal expected allele frequency for a pathogenic variant in COL1A1 causing Osteogenesis Imperfecta phenotype (2.8e-05), strongly suggesting that the variant is a benign polymorphism. Though the variant c.1984-5C>A (also called as IVS29-5C>A) has been reported in the literature in individuals affected with Osteogenesis Imperfecta (Venturi_2006, Schleit_2015), no strong evidence for causality was provided. These reports therefore do not provide unequivocal conclusions about association of the variant with Osteogenesis Imperfecta. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine submitters have provided clinical-significance assessments for this variant in ClinVar after 2014 without evidence for independent evaluation, and classified the variant as VUS (1x), likely benign (3x) or benign (5x). Based on the evidence outlined above, the variant was classified as benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000177437 SCV001809020 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000177437 SCV001929784 benign not specified no assertion criteria provided 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.