Submissions for variant NM_000093.5(COL5A1):c.4554+4C>T

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002340172	SCV002637251	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2019-06-24	criteria provided, single submitter	clinical testing	The c.4554+4C>T intronic variant results from a C to T substitution 4 nucleotides after coding exon 58 in the COL5A1 gene. This nucleotide position is poorly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor/donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Neuberg Centre For Genomic Medicine, NCGM	RCV004577016	SCV005061049	uncertain significance	Ehlers-Danlos syndrome, classic type, 1		criteria provided, single submitter	clinical testing	The observed splice region / intronic c.4554+4C>T variant in COL5A1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency of 0.001% in the gnomAD Exomes. This variant has been reported to the ClinVar database as Uncertain Significance. However, no details are available for independent assessment. This splice region variant in intron 58 affects the position six nucleotides downstream of exon 57. The spliceAI tool predicts that this splice site variant is benign. For these reasons, this variant has been classified as Uncertain Significance.