ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.3525+19del (rs138061246)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181062 SCV000233338 benign Familial thoracic aortic aneurysm and aortic dissection 2013-01-17 criteria provided, single submitter clinical testing The variant is found in TAAD panel(s).
PreventionGenetics,PreventionGenetics RCV000242246 SCV000302044 benign not specified criteria provided, single submitter clinical testing
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000659430 SCV000781244 likely benign Connective tissue disease 2016-11-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000242246 SCV001361057 benign not specified 2019-08-19 criteria provided, single submitter clinical testing Variant summary: COL3A1 c.3525+19delG alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 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 0.0099 in 228966 control chromosomes, predominantly at a frequency of 0.016 within the Non-Finnish European subpopulation in the gnomAD database, including 14 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 12800-folds over the estimated maximal expected allele frequency for a pathogenic variant in COL3A1 causing Aortopathy phenotype (1.3e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.3525+19delG in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission (evaluation after 2014) cites the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.

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