---
license: apache-2.0
tags:
- biology
- genomics
- dna
- variant-effect-prediction
---

# VEP consequences with CRE annotations for all possible SNVs in the human genome hg38

Pre-computed VEP consequences for all possible single nucleotide variants (SNVs) in the human genome (GRCh38/hg38), with cis-regulatory element (CRE) annotations from ENCODE SCREEN.

Code: https://github.com/gonzalobenegas/hg38-variant-consequences

## Dataset Details

- **VEP container:** `docker://ensemblorg/ensembl-vep:release_109.1`
- **VEP flags:** `--most_severe --distance 1000`
- **CRE source:** [ENCODE SCREEN](https://screen.wenglab.org/)

## CRE Annotation

For non-exonic variants (intergenic, intronic, upstream/downstream gene variants), the `consequence_cre` column contains the CRE class based on overlap with cis-regulatory elements:

| CRE Class | Description |
|-----------|-------------|
| PLS | Promoter-like signature |
| pELS | Proximal enhancer-like signature |
| dELS | Distal enhancer-like signature |
| CA-H3K4me3 | Chromatin accessible + H3K4me3 |
| CA-CTCF | Chromatin accessible + CTCF |
| CA-TF | Chromatin accessible + TF |
| CA | Chromatin accessible only |
| TF | TF binding only |

Variants within 500bp of a CRE (but not overlapping the core) are annotated with the `_flank` suffix (e.g., `PLS_flank`).

Priority order: core annotations override flank annotations; within each category, earlier classes in the table take precedence.

## Schema

| Column | Type | Description |
|--------|------|-------------|
| chrom | String | Chromosome (1-22, X, Y) |
| pos | UInt32 | Position (1-based) |
| ref | String | Reference allele |
| alt | String | Alternate allele |
| consequence | String | Most severe VEP consequence (original) |
| consequence_cre | String | Consequence with CRE class for non-exonic variants |

For exonic variants, `consequence` and `consequence_cre` are identical. For non-exonic variants overlapping CREs, `consequence_cre` contains the CRE class while `consequence` retains the original VEP annotation.

Files are sorted by `(chrom, pos, ref, alt)`.

## Download

### Using Hugging Face CLI

```bash
pip install -U huggingface_hub
hf download songlab/hg38-variant-consequences --repo-type dataset
```

This downloads to `./hg38-variant-consequences/`.

### Using wget

```bash
wget https://huggingface.co/datasets/songlab/hg38-variant-consequences/resolve/main/{1..22}.parquet
wget https://huggingface.co/datasets/songlab/hg38-variant-consequences/resolve/main/{X,Y}.parquet
```

## Usage with Polars

The recommended approach for joining variants with consequences is a per-chromosome loop with streaming. This avoids memory issues when working with the large annotation files.

```python
import polars as pl

VARIANTS_PATH = "variants.parquet"
CONSEQUENCES_DIR = "hg38-variant-consequences"
CHROMS = [str(i) for i in range(1, 23)] + ["X", "Y"]
```

### Example 1: Small variants file (load into memory)

```python
variants = pl.read_parquet(VARIANTS_PATH)

results = []
for chrom in CHROMS:
    chrom_variants = variants.filter(pl.col("chrom") == chrom)
    consequences_lf = pl.scan_parquet(f"{CONSEQUENCES_DIR}/{chrom}.parquet")

    joined = chrom_variants.lazy().join(
        consequences_lf,
        on=["chrom", "pos", "ref", "alt"],
        how="left",
        maintain_order="left",
    ).collect(engine="streaming")

    results.append(joined)

final = pl.concat(results)
```

### Example 2: Large variants file (stream from disk)

For variants files with millions of rows, keep both sides lazy:

```python
results = []
for chrom in CHROMS:
    consequences_lf = pl.scan_parquet(f"{CONSEQUENCES_DIR}/{chrom}.parquet")

    joined = pl.scan_parquet(VARIANTS_PATH).filter(
        pl.col("chrom") == chrom
    ).join(
        consequences_lf,
        on=["chrom", "pos", "ref", "alt"],
        how="left",
        maintain_order="left",
    ).collect(engine="streaming")

    results.append(joined)

final = pl.concat(results)
```