A subjective classification of the severity of the variant consequence. The four categories are:
The variant is assumed to have high (disruptive) impact in the protein, probably causing protein truncation, loss of function or triggering nonsense mediated decay.
A non-disruptive variant that might change protein effectiveness.
Assumed to be mostly harmless or unlikely to change protein behaviour.
Usually non-coding variants or variants affecting non-coding genes, where predictions are difficult or there is no evidence of impact.