Variants found in exons with a median depth < 1 were removed from both counts.
The O/E constraint score is the ratio of the observed/expected variants in that gene. Each item in this track shows the O/E ratio for three different types of variation: missense, synonymous, and loss-of-function. The O/E ratio is a continuous measurement of how tolerant a gene or transcript is to a certain class of variation. When a gene has a low O/E value, it is under stronger selection for that class of variation than a gene with a higher O/E value. Because Counts depend on gene size and sample size, the precision of the values varies a lot from one gene to the next. Therefore, the 90% confidence interval (CI) is also displayed along with the O/E ratio to better assist interpretation of the scores.
When evaluating how constrained a gene is, it is essential to consider the CI when using O/E. In research and clinical interpretation of Mendelian cases, pLI > 0.9 has been widely used for filtering. Accordingly, the Gnomad team suggests using the upper bound of the O/E confidence interval -LOEUF < 0.35 as a threshold if needed. +LOEUF < 0.45 as a threshold if needed (this was <0.35 prior to v4.1.1, see Methods below).
Please see the Methods section below for more information about how the scores were calculated.
The pLI and Z-scores of the deviation of observed variant counts relative to the expected number are intended to measure how constrained or intolerant a gene or transcript is to a specific type of variation. Genes or transcripts that are particularly depleted of a specific class of variation (as observed in the gnomAD data set) are considered intolerant of that specific type of variation. Z-scores are available for the missense and synonymous categories and pLI scores are available for the loss-of-function variation.
Missense and Synonymous: Positive Z-scores indicate more constraint (fewer observed