Submissions for variant NM_000090.4(COL3A1):c.1815+5G>A

gnomAD frequency: 0.00023  dbSNP: rs146652498

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000176519	SCV000228188	likely benign	not specified	2015-04-24	criteria provided, single submitter	clinical testing
GeneDx	RCV000589672	SCV000521083	likely benign	not provided	2021-02-05	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26332594, 22001912, 30115950, 31141158, 32123317)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000986955	SCV000554713	benign	Ehlers-Danlos syndrome, type 4	2025-01-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000176519	SCV000603141	uncertain significance	not specified	2017-01-06	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589672	SCV000695356	benign	not provided	2017-06-12	criteria provided, single submitter	clinical testing	Variant summary: The COL3A1 c.1815+5G>A variant involves the alteration of a conserved intronic nucleotide and 4/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 74/121588 control chromosomes at a frequency of 0.0006086, which is approximately 487 times the estimated maximal expected allele frequency of a pathogenic COL3A1 variant (0.0000013), suggesting this variant is likely a benign polymorphism, along with multiple clinical diagnostic laboratories classified this variant as likely benign/likely benign. Taken together, this variant is classified as benign.
Ambry Genetics	RCV000776194	SCV000738509	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2017-02-24	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659418	SCV000781231	uncertain significance	Connective tissue disorder	2016-11-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000776194	SCV000911323	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-10-08	criteria provided, single submitter	clinical testing
Mendelics	RCV000986955	SCV001136117	benign	Ehlers-Danlos syndrome, type 4	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000986955	SCV001296608	benign	Ehlers-Danlos syndrome, type 4	2018-06-13	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277377	SCV002565610	likely benign	Ehlers-Danlos syndrome	2021-02-23	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000776194	SCV003838685	benign	Familial thoracic aortic aneurysm and aortic dissection	2021-08-11	criteria provided, single submitter	clinical testing