the different assays. For example, the effect on the luciferase activity could be larger due to both the degradation of the mRNA and the blockade of translation. In contrast, the effect on the protein levels and activity could be smaller due to delays from the time of changes in mRNA levels until the changes in protein levels and activities are observed. Typically, changes in mRNA expression due to endogenous miRNA-mediated regulation are subtle (<30%) (Baek et al., 2008; Bartel, 2009; Denzler et al., 2016). Consequently one would expect relatively small effect sizes of the variants, which was what was seen in many of these variants. However, there are many examples demonstrating the clinical impact of these types of variants (Bhattacharya et al., 2014).
