Submissions for variant NM_000350.3(ABCA4):c.5714+5G>T

dbSNP: rs61751407

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000498660	SCV000589731	likely pathogenic	not provided	2016-01-26	criteria provided, single submitter	clinical testing	The c.5714+5 G>T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.5714+5 G>T variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Several in-silico splice prediction models predict that c.5714+5 G>T either destroys or damages the natural donor site and lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae	RCV000498660	SCV003211235	uncertain significance	not provided	2022-07-06	criteria provided, single submitter	clinical testing	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. This variant disrupts the c.5714+5G nucleotide in the ABCA4 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 9466990, 10413692, 19074458). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 432057). This variant has been observed in individual(s) with ABCA4-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 40 of the ABCA4 gene. It does not directly change the encoded amino acid sequence of the ABCA4 protein. It affects a nucleotide within the consensus splice site.