---
license: other
license_name: ensembl-unrestricted-and-loftee-mit
license_details: Ensembl data are freely available without restriction; LOFTEE resources are from an MIT-licensed project. See the Licensing section below.
language:
- en
tags:
- genomics
- ensembl
- vep
- loftee
- GRCh38
- reference-data
pretty_name: VEP 113 GRCh38 reference bundle (cache, FASTA, LOFTEE)
---

# VEP 113 / GRCh38 reference bundle — cache, FASTA, LOFTEE data

A fast mirror of the reference data needed to run Ensembl VEP release 113
offline on GRCh38, in the prepared forms a local annotation pipeline needs —
assembled for the **WES/WGS diagnostic analysis pipeline** (IEI variant-review
workbench), whose downloader verifies every file against pinned SHA-256
checksums and falls back to the canonical sources automatically.

Mirror rationale: the canonical servers often serve well under 1 MiB/s per
connection transatlantically; this mirror typically saves hours on first-time
setup. Contents are unmodified from their sources except where noted.

## Files

| File | Contents | Source |
|---|---|---|
| `homo_sapiens_vep_113_GRCh38.cache.tar.gz` | Ensembl VEP indexed cache, release 113, GRCh38 (retarred from the extracted official cache) | Ensembl |
| `Homo_sapiens.GRCh38.dna.primary_assembly.fa.gz` (+ `.fai`, `.gzi`) | GRCh38 primary-assembly FASTA, **re-compressed as BGZF** with indexes (VEP/LOFTEE require BGZF; Ensembl ships plain gzip) | Ensembl |
| `human_ancestor.fa.gz` (+ `.fai`, `.gzi`) | LOFTEE GRCh38 ancestral sequence | LOFTEE (Broad) |
| `loftee.sql` | LOFTEE GRCh38 conservation database | LOFTEE (Broad) |
| `gerp_conservation_scores.homo_sapiens.GRCh38.bw` | GERP conservation bigWig for LOFTEE GRCh38 | Ensembl/LOFTEE |

## Licensing and attribution

- **Ensembl data** (VEP cache, FASTA, GERP bigWig): Ensembl data are freely
  available without restriction; see https://www.ensembl.org/info/about/legal/disclaimer.html.
  Cite: McLaren et al., *The Ensembl Variant Effect Predictor*, Genome
  Biology 17, 122 (2016), and the current Ensembl release paper.
- **LOFTEE data** (ancestral FASTA, conservation SQL): from the public LOFTEE
  resources (MIT-licensed project); cite Karczewski et al., Nature 581,
  434–443 (2020). https://github.com/konradjk/loftee
- This compilation adds no restrictions.

## Use with the pipeline

`scripts/download_references.sh` uses this mirror automatically when
configured, verifying each file against the SHA-256 checksums pinned in the
script and falling back to the canonical Ensembl/Broad sources if the mirror
is unavailable or fails verification. Manual use: download, verify, then
place the files under your configured reference locations (`vep_cache/` for
the extracted tarball, `fasta/`, `loftee/`).