How does Emedgene Analyze prioritize transcripts?

Scope

Emedgene uses VEP and EFF for transcript annotations and in upcoming versions will be adding Illumina Connected Annotations.

Each variant has a "main_effect" and "main_gene" chosen based on the most prioritized transcript for this variant. Transcript prioritization depends on many different parameters and on different Emedgene pipeline versions.

Transcript prioritization in V37.0

Here is a list of ordered rules for transcript prioritization:

1. VEP transcripts are prioritized over EFF transcripts.

2. If the case is a virtual panel, prioritize transcripts from genes in the case gene list (but not for Boosted Genes type panels).

3. Prioritize RNA genes associated with disease (See appendix 1 for prioritized list RNA genes). Importantly this does not apply to upstream and downstream RNA variants.

4. De-prioritize biotype readthrough transcripts.

5. Prioritize based on impact in the following order: HIGH > MODERATE > LOW > MODIFIER.

6. Prioritize introns over UTR over upstream (Appendix 2: MODIFIER effects prioritization).

7. Prioritize organization canonical transcripts (Defined in Curate. Always applied, no settings needed).

8. Prioritize canonical transcripts (Based on Appris).

9. Prioritize transcripts from genes in the case gene list.

10. Prioritizing gene without “-” in their Name.

Transcript prioritization < V37.0

Here is a list of ordered rules for transcript prioritization:

1. VEP transcripts are prioritized over EFF transcripts.

2. If the case is a virtual panel, prioritize transcripts from genes in the case gene list (but not for Boosted Genes type panels).

3. Prioritize RNA genes associated with disease (See appendix 1 for prioritized list RNA genes). Importantly this does not apply to upstream and downstream RNA variants.

4. De-prioritize biotype readthrough transcripts.

5. Prioritize based on impact in the following order: HIGH > MODERATE > LOW > MODIFIER.

6. Prioritize introns over UTR over upstream (Appendix 2: MODIFIER effects prioritization).

7. Prioritize organization canonical transcripts (Defined in Curate, this parameter has to be implemented upon request.).

8. Prioritize canonical transcripts (Based on Appris).

Appendixes

Appendix 1: List of RNA genes associated with disease

ATXN8OS, GNAS-AS1, H19, HELLPAR, KCNQ1OT1, LINC00237, LINC00299, MEG3, MIAT, MIR137, MIR140, MIR184, MIR19B1, MIR204, MIR2861, MIR4718, MIR605, MIR96, MIR99A, RMRP, RNU12, RNU4-2*, RNU4ATAC, RNU7-1*, SNORD116-1, SNORD118, TERC, MT-TF, MT-RNR1, MT-TV, MT-RNR2, MT-TL1, MT-TI, MT-TQ, MT-TM, MT-TW, MT-TA, MT-TN, MT-TC, MT-TY, MT-TS1, MT-TD, MT-TK, MT-TG, MT-TR, MT-TH, MT-TS2, MT-TL2, MT-TE, MT-TT, MT-TP.

*Added as part of pipeline V35.2

Appendix 2: MODIFIER effects prioritization

Order of modifier effects:

• intron_variant

• 5_prime_utr_variant

• 3_prime_utr_variant

• non_coding_transcript_exon_variant

• non_coding_transcript_variant

• upstream_gene_variant

• downstream_gene_variant

• All others effects

Keywords for search

How transcripts are being prioritized?

How transcripts are being selected/choosen?

Why is this gene selected for this variant?

Why I can't choose a transcript?

Why my transcript is missing for this variant?

My gene is missing in the transcript list.