Description
Variant summary: MEFV c.540G>C results in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 6.6e-06 in 150946 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. Though c.540G>C has been reported in the literature in some Turkish individuals affected with Familial Mediterranean Fever, authors listed the variant as a polymorphism (Berdeli 2011, Nalbantoglu 2013). In addition, co-occurrences with two other pathogenic variants have been reported in patients (Infever database: MEFV p.Met694Val / p.Met694Val and p.Met694Val / p.Val726Ala), and co-occurrence with another pathogenic MEFV variant (p.Met694Val) was also reported in an asymptomatic individual (Karakose 2017), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
