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

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

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