ClinVar Miner

Submissions for variant NM_000038.5(APC):c.835-4T>G (rs756807560)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc RCV000659271 SCV000781067 likely pathogenic Familial adenomatous polyposis 2016-11-01 criteria provided, single submitter clinical testing
Color RCV000776476 SCV000912030 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-07 criteria provided, single submitter clinical testing
GeneDx RCV000482851 SCV000571299 uncertain significance not provided 2016-08-12 criteria provided, single submitter clinical testing This variant is denoted APC c.835-4T>G or IVS8-4T>G and consists of a T>G nucleotide substitution at the -4 position of intron 8 of the APC gene. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. In silico models are inconclusive with respect to splicing, and in the absence of RNA or functional studies, the actual effect of this variant is unknown. APC c.835-4T>G was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The thymine (T) nucleotide that is altered is not conserved across species. Based on currently available information, it is unclear whether APC c.835-4T>G is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000542810 SCV000647769 uncertain significance Familial adenomatous polyposis 1 2018-03-28 criteria provided, single submitter clinical testing This sequence change falls in intron 8 of the APC gene. It does not directly change the encoded amino acid sequence of the APC protein. This variant is present in population databases (rs756807560, ExAC 0.006%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 421952). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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