> For the complete documentation index, see [llms.txt](https://help.connected.illumina.com/llms.txt). Markdown versions of documentation pages are available by appending `.md` to page URLs; this page is available as [Markdown](https://help.connected.illumina.com/annotation/introduction/readme.md). # About Illumina Connected Annotations 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. {% hint style="info" %} **Start here** * [Quick start guidance on Illumina Connected Annotations v3.27.](/annotation/v3.27/introduction/readme.md) {% endhint %} ### What does Illumina Connected Annotations annotate? Illumina Connected Annotations uses Sequence Ontology consequences to describe transcript impact.
Variant consequence overview

Transcript consequences are reported using Sequence Ontology terms.

### Software Download Please visit [Illumina Connected Annotations](https://developer.illumina.com/illumina-connected-annotations). ### Reference genome support Illumina Connected Annotations supports `GRCh37.p13` and `GRCh38.p14`. * Review the `GRCh37.p13` chromosome and contig list in the [assembly report](https://ftp.ncbi.nlm.nih.gov/genomes/all/annotation_releases/9606/105.20220307/GCF_000001405.25_GRCh37.p13/GCF_000001405.25_GRCh37.p13_assembly_report.txt) * Review the `GRCh38.p14` chromosome and contig list in the [assembly report](https://ftp.ncbi.nlm.nih.gov/genomes/all/annotation_releases/9606/GCF_000001405.40-RS_2023_10/GCF_000001405.40_GRCh38.p14_assembly_report.txt) {% hint style="warning" %} 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. {% endhint %}
Details on the earlier GRCh38 reference issue Previous releases used GRCh38.p13 contig names from [109.20190607](https://ftp.ncbi.nlm.nih.gov/genomes/all/annotation_releases/9606/109.20190607/GCF_000001405.39_GRCh38.p13/GCF_000001405.39_GRCh38.p13_assembly_report.txt) with FASTA sequence from GRCh38.p12 [109](https://ftp.ncbi.nlm.nih.gov/genomes/all/annotation_releases/9606/109/GCF_000001405.38_GRCh38.p12/). 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](https://ftp.ncbi.nlm.nih.gov/genomes/all/annotation_releases/9606/) and [Ensembl](https://ftp.ensembl.org/pub/). 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 | {% hint style="info" %} 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. {% endhint %} Gene symbols are sourced from [HGNC](https://ftp.ebi.ac.uk/pub/databases/genenames/hgnc/json/hgnc_complete_set.json) as of `2024-06-03`. Use [Data Manager](/annotation/v3.27/utilities/data-manager.md) 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](/annotation/v3.27/introduction/licensedcontent.md). For access, contact `annotation_support@illumina.com`.
Data SourceAvailabilityLatest Supported Version (v3.27)
COSMICProfessional102
OMIMProfessional20250815
✨ PrimateAI-3DProfessional1.0
✨ PromoterAIProfessional1.0
✨ SpliceAIProfessional1.3
1000 Genomes ProjectBasicPhase 3 v3plus
ABraOMBasicSABE-WGS-1171
AlphaMissenseBasic1.0
Amino Acid ConservationBasic1.0
Cancer HotspotsBasic2017
ClinGenBasic20250815
ClinVarBasic20250806
ClinVar PreviewBasic20250601
DANNBasic20200205
dbSNPBasic156
DECIPHERBasic201509
FusionCatcherBasic1.33
GERPBasic20110522
GME VariomeBasic20160618
gnomADBasic

GRCh37 - v2.1

GRCh38 - v4.1

Mitochondrial HeteroplasmyBasic20180410
MITOMAPBasic20200819
MultiZ 100 WayBasic20171006
PhyloP PrimateBasic1.0
REVELBasic20200205
TOPMedBasicfreeze 5
### Data management Use [Data Manager](/annotation/v3.27/utilities/data-manager.md) to: * list supported versions * download annotation files * validate local data --- # Agent Instructions This documentation is published with GitBook. GitBook is the documentation platform designed so that both humans and AI agents can read, navigate, and reason over technical content effectively. Learn more at gitbook.com. ## Querying This Documentation If you need additional information that is not directly available in this page, you can query the documentation dynamically by asking a question. Perform an HTTP GET request on the current page URL with the `ask` query parameter, and the optional `goal` query parameter: ``` GET https://help.connected.illumina.com/annotation/introduction/readme.md?ask=&goal= ``` `ask` is the immediate question: it should be specific, self-contained, and written in natural language. `goal` is optional and describes the broader end goal you are ultimately trying to accomplish on behalf of the user. GitBook uses it to tailor the answer towards what is most useful for that goal. The response will contain a direct answer to the question and relevant excerpts and sources from the documentation. Use this mechanism when the answer is not explicitly present in the current page, you need clarification or additional context, or you want to retrieve related documentation sections.