ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.897+4A>G

gnomAD frequency: 0.00001  dbSNP: rs886039191
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002311221 SCV000320584 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2015-12-20 criteria provided, single submitter clinical testing The c.897+4A>G intronic variant results from an A to G substitution 4 nucleotides downstream of coding exon 12 in the COL3A1 gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This nucleotide position is highly conserved in available vertebrate species. Using two different splice site prediction tools, this alteration is predicted by BDGP to abolish the native splice donor site, and is predicted to weaken (but not abolish) the efficiency of the native splice donor site by ESEfinder; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
CeGaT Center for Human Genetics Tuebingen RCV001171819 SCV001334686 uncertain significance not provided 2020-03-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003522951 SCV004364526 uncertain significance Ehlers-Danlos syndrome, type 4 2024-01-08 criteria provided, single submitter clinical testing This sequence change falls in intron 12 of the COL3A1 gene. It does not directly change the encoded amino acid sequence of the COL3A1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 264567). 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.
All of Us Research Program, National Institutes of Health RCV003522951 SCV004833777 uncertain significance Ehlers-Danlos syndrome, type 4 2023-08-23 criteria provided, single submitter clinical testing This variant causes an A to G nucleotide substitution at the +4 position of intron 12 of the COL3A1 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with COL3A1-related disorders in the literature. This variant has been identified in 1/31354 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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