About Illumina Connected Annotations

Translational research-grade variant annotation

Illumina Connected Annotations provides translational research-grade variant annotation from AI models and traditional sources for genomic data.

It annotates SNVs, MNVs, insertions, deletions, indels, STRs, gene fusions, and structural variants, including CNVs. You can run it as a standalone package or embed it in larger workflows.

Inputs are VCF files. Outputs are structured JSON or optional VCF. JSON is the default and most complete output format. VCF output supports a reduced annotation set.

Illumina Connected Annotations supports multi-allelic and multi-sample VCFs. It is developed under a rigorous software development lifecycle (SDLC) process with continuous validation against large baseline annotation sets.

Start here

• Set up the standalone package in Getting Started with local download
• Use the DRAGEN workflow in Getting Started with DRAGEN
• Review Licensed Content for premium sources

What does Illumina Connected Annotations annotate?

Illumina Connected Annotations uses Sequence Ontology consequences to describe transcript impact.

Transcript consequences are reported using Sequence Ontology terms.

Reference genome support

Illumina Connected Annotations supports GRCh37.p13 and GRCh38.p14.

• Review the GRCh37.p13 chromosome and contig list in the assembly report
• Review the GRCh38.p14 chromosome and contig list in the assembly report

Use GRCh38.p14 for new work.

Earlier GRCh38 releases had an alt-contig naming mismatch. This affected variant IDs and HGVS g. notation on some alt contigs. Main chromosomes were not affected.

Details on the earlier GRCh38 reference issue

Previous releases used GRCh38.p13 contig names from 109.20190607 with FASTA sequence from GRCh38.p12 109. This created mismatches for some alt contigs.

GRCh38.p14 fixes this issue and remains backward compatible with older transcript, gene model, and supplementary annotation files.

Transcript and gene models

Transcript consequences depend on the selected RefSeq or Ensembl release.

Illumina Connected Annotations uses gene models from RefSeq and Ensembl. The currently supported versions for GRCh38 are:

Data Source	Version	Release Date
RefSeq	GCF_000001405.40-RS_2024_08	2024-08-26
RefSeq	GCF_000001405.40-RS_2023_10	2023-10-07
RefSeq	GCF_000001405.40-RS_2023_03	2023-03-21
Ensembl	113	2024-10-18
Ensembl	112	2024-05-14
Ensembl	110	2023-04-27
Ensembl	108	2022-10-20

For GRCh37:

Data Source	Version	Release Date
RefSeq	105.20220307	2022-03-10
Ensembl	110	2023-02-08
Ensembl	108	2022-10-20

For GRCh37, Ensembl release 110 is effectively the same annotation set as release 87.

NCBI no longer publishes new GRCh37 RefSeq gene annotation releases. 105.20220307 is the final GRCh37 RefSeq release.

Gene symbols are sourced from HGNC as of 2024-06-03.

Use Data Manager to list supported versions and download them.

Supplementary annotations

Illumina Connected Annotations adds external data sources for variant and gene context.

Content is available in two tiers:

• Basic — available without a premium license
• Professional — requires a license

For licensing details, see Licensed Content. For access, contact [e-mail].

Data Source	Availability	Latest Supported Version
COSMIC	Professional	102
OMIM	Professional	20250815
✨ PrimateAI-3D	Professional	1.0
✨ PromoterAI	Professional	1.0
✨ SpliceAI	Professional	1.3
1000 Genomes Project	Basic	Phase 3 v3plus
ABraOM	Basic	SABE-WGS-1171
AlphaMissense	Basic	1.0
Amino Acid Conservation	Basic	1.0
Cancer Hotspots	Basic	2017
ClinGen	Basic	20250815
ClinVar	Basic	20250806
ClinVar Preview	Basic	20250601
DANN	Basic	20200205
dbSNP	Basic	156
DECIPHER	Basic	201509
FusionCatcher	Basic	1.33
GERP	Basic	20110522
GME Variome	Basic	20160618
gnomAD	Basic	GRCh37 - v2.1 GRCh38 - v4.1
Mitochondrial Heteroplasmy	Basic	20180410
MITOMAP	Basic	20200819
MultiZ 100 Way	Basic	20171006
PhyloP Primate	Basic	1.0
REVEL	Basic	20200205
TOPMed	Basic	freeze 5

Data management

Use Data Manager to:

• list supported versions
• download annotation files
• validate local data

Download

Please visit Illumina Connected Annotations.