Table 1 Step A: functional grading.
From: Stepwise ABC system for classification of any type of genetic variant
Functional classes | Score | ~Odds | Description | |
|---|---|---|---|---|
fVUS | Variant of unknown functional significance—a functional VUS or fVUS | 0 | Variant of unknown functional significance—usually due to the lack of knowledge | |
NF | Normal function (NF) | 1 | <1% | High-frequency variant with no reason to suspect a recessive or hypomorphic role |
LNF | Likely normal function (LNF) | 2 | 1–10% | Moderate-frequency variant with no reason to suspect a recessive or hypomorphic role |
HFE | Hypothetical functional effect (HFE) | 3 | 50–90% | Rare variant that could affect gene function based on biological knowledge and bioinformatic tools |
LFE | Likely functional effect (LFE), or Hypomorphic variant (in recessive disease) | 4 | 90–99% | Recessive: variant that reduces gene function, but that only causes a biochemical abnormality or disease if in trans to a LoF allele Dominant: likely LoF, or variant of likely functional importance |
FE | Functional effect (FE) | 5 | >99% | Variant that disrupt gene function (certain LoF) or known to be disease causing (known GoF or dominant-negative effect) |
