Description

The GREGoR Consortium (Genomics Research to Elucidate the Genetics of Rare diseases) is a National Human Genome Research Institute (NHGRI)-funded research consortium that works to identify the genetic basis of currently unexplained rare diseases. GREGoR is a collaboration between multiple research centers and a data coordinating center that apply genomic technologies to rare disease cohorts.

This track shows allele frequencies from the GREGoR Release 4 (R04, October 2025) joint variant callset of a subset of the 10,683 participants across 4,366 families. The joint callset includes only the 8,161 short-read whole-genome sequencing (WGS) samples, or a subset of these. The GREGoR site does not specify how many samples exactly are part of the joint callset. The callset does not include any of the 2,629 whole-exome sequencing (WES) samples. GREGoR also provides some long-read WGS, RNA-seq, and ATAC-seq, but these were not used for the joint callset either. The VCF shown here contains variant calls with VEP consequence annotations. The INFO fields include allele count (AC), allele frequency (AF), allele number (AN), and counts broken down by affected status (AC_AFFECTED, AC_UNAFFECTED, AC_UNKNOWN).

Display Conventions

This is a VCF track. When zoomed in, variants are displayed with base-specific coloring. Mouseover shows the variant position, alleles, and allele frequency.

Data Access

The data can be explored interactively with the Table Browser or the Data Integrator. For programmatic access, our REST API can be used; the track name is gregor. For bulk download, the VCF file can be obtained from our download server.

The full controlled-access GREGoR data is available through the AnVIL platform via controlled dbGaP access. More information on data access is available at the GREGoR data page.

Methods

The sample processing methods of the GREGoR project depend on the sequencing center, see the Methods document below for details. The GREGoR R04 joint callset for short-read whole genome sequencing (srWGS) was generated by the GREGoR Data Coordinating Center (DCC) through a two-stage harmonization and joint genotyping pipeline. Raw srWGS data from GREGoR Consortium Research Centers were uniformly reprocessed with the Whole Genome Germline Single Sample WARP pipeline in DRAGEN-GATK mode (v3.1.6). This pipeline aligns reads to the GRCh38 reference genome (GCA_000001405.15_GRCh38_no_alt_analysis_set) with the DRAGMAP aligner, marks duplicates with Picard v2.26.10, and performs single-sample variant calling with GATK HaplotypeCaller using the DragSTR model with hard filtering. The output is per-sample gVCFs. Joint variant calling across all harmonized samples was then performed with the Genomic Variant Store (GVS), a scalable cloud-native joint genotyping pipeline developed for large cohort analysis in which variants are ingested into a query-optimized store and rendered to a multi-sample variant file format. The resulting joint callset was functionally annotated with Ensembl Variant Effect Predictor (VEP) v112. Full methods, with per-site library preparation and bioinformatics pipelines for independently processed samples, are available in the GREGoR R04 Methods document.

At UCSC, site VCF files were downloaded from GREGoR's Google Drive. The VCFs were merged with bcftools. We provide documentation that indicates how all source files of the varFreqs track were converted in the makeDoc file of the track. For some tracks, python scripts were necessary and are also available from GitHub

Credits

The GREGoR Consortium is supported by the National Human Genome Research Institute (NHGRI). We thank the participants, their families, and the consortium for making this data available. For more information, see the GREGoR About page.

References

The GREGoR Consortium does not yet have a peer-reviewed flagship publication describing the R04 release. For methods and data access details, see the GREGoR R04 Methods document and the GREGoR Consortium website.