19b8bfeadc8dc28380404a15e39ba662040dd279 gperez2 Thu Jul 30 09:27:03 2026 -0700 Adding v4.1.1 to gnomad.html's Constraint Metrics bullet, and updating gnomadPLI.html's general LOEUF threshold recommendation from <0.35 to <0.45. refs #37351 diff --git src/hg/makeDb/trackDb/human/hg38/gnomadPLI.html src/hg/makeDb/trackDb/human/hg38/gnomadPLI.html index 48147b6eafe..a8c56be6841 100644 --- src/hg/makeDb/trackDb/human/hg38/gnomadPLI.html +++ src/hg/makeDb/trackDb/human/hg38/gnomadPLI.html @@ -66,31 +66,31 @@ <p> Variants found in exons with a median depth < 1 were removed from both counts. <p> 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. <b>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.</b> 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. <p> When evaluating how constrained a gene is, <b>it is essential to consider the CI when using O/E</b>. In research and clinical interpretation of Mendelian cases, <b>pLI > 0.9</b> has been widely used for filtering. Accordingly, the Gnomad team suggests using the upper bound of the O/E confidence interval -<b>LOEUF < 0.35</b> as a threshold if needed. +<b>LOEUF < 0.45</b> as a threshold if needed (this was <0.35 prior to v4.1.1, see Methods below). <p> Please see the Methods section below for more information about how the scores were calculated. </p> <h3>pLI and Z-scores</h3> <p> 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. </p> <p> <em>Missense and Synonymous</em>: Positive Z-scores indicate more constraint (fewer observed