GnomAD Genome Mutational Constraint, also known as "Genome non-coding constraint of haploinsufficient variation (Gnocchi)", is based on v3.1.2 and is available only on hg38. It shows the reduced variation caused by purifying natural selection. This is similar to negative selection on loss-of-function (LoF) for genes, but can be calculated for non-coding regions too. Positive values are red and reflect stronger mutation constraint (and less variation), indicating higher natural selection pressure in a region. Negative values are green and reflect lower mutation constraint (and more variation), indicating less selection pressure and less functional effect. Briefly, for any 1kbp window in the genome, a model based on trinucleotide sequence context, base-level methylation, and regional genomic features predicts expected number of mutations, and compares this number to the observed number of mutations using a Z-score (see Chen et al 2024 in the Reference section for details). The chrX scores were added as received from the authors, as there are no de novo mutation data available on chrX (for estimating the effects of regional genomic features on mutation rates), they are more speculative than the ones on the autosomes.
The raw data can be explored interactively with the Table Browser, or the Data Integrator. For automated analysis, the data may be queried from our REST API, and the genome annotations are stored in files that can be downloaded from our download server, subject to the conditions set forth by the gnomAD consortium (see below).
The mutational constraints score was updated in October 2022 from a previous, now deprecated, pre-publication version. The old version can be found in our archive directory on the download server. It can be loaded by copying the URL into our "Custom tracks" input box.
The data can also be found directly from the gnomAD downloads page. Please refer to our mailing list archives for questions, or our Data Access FAQ for more information.
Thanks to the Genome Aggregation Database Consortium for making these data available. The data are released under the Creative Commons Zero Public Domain Dedication as described here.
Please note that some annotations within the provided files may have restrictions on usage. See here for more information.
Chen S, Francioli LC, Goodrich JK, Collins RL, Kanai M, Wang Q, Alföldi J, Watts NA, Vittal C, Gauthier LD et al. A genomic mutational constraint map using variation in 76,156 human genomes. Nature. 2024 Jan;625(7993):92-100. PMID: 38057664