Transcript prioritization logic
Each variant has a main_effect and main_gene chosen based on the most prioritized transcript for this variant. This selection influences how variants are displayed, interpreted and classified across the platform.
From v39.0+, Emedgene introduces improvements to Curate transcript prioritization and updates the RNA gene prioritization logic.
Transcript prioritization (v39.0+)
Emedgene uses VEP and EFF for transcript annotations and supports organization-defined canonical and preferred transcripts from Curate.
VEP transcripts are prioritized over EFF transcripts.
If the case is a Virtual Panel, prioritize transcripts from genes in the case gene list (not applied for Boosted Genes panel types).
Prioritize transcripts defined in Curate variants
Curate variant-level preferred transcripts now receive high priority.
Requires the new organization setting, enabled by Illumina Bioinformatics support.
Prioritize RNA genes associated with disease
(See Appendix 1: Updated RNA gene list)
This rule does not apply to upstream or downstream RNA variants.
RNA gene prioritization has been refined in v39.0.
De-prioritize readthrough biotype transcripts.
Prioritize intronic based on variant impact:
HIGH → MODERATE → LOW → MODIFIER
Prioritize intronic > UTR > upstream effects
(See Appendix 2 for MODIFIER effect prioritization)
Prioritize organization canonical transcripts
Defined in Curate
Always applied; no additional settings required
Prioritize canonical transcripts based on APPRIS.
Prioritize transcripts from genes in the case gene list.
Prioritize genes without a " — " in their symbol.
Note: Curate transcript prioritization is available only for organizations that request the setting through Illumina Bioinformatics Support in v39.0.
RNA gene prioritization (v39.0+)
From version 39.0, Emedgene has changed how RNA genes are prioritized relative to protein-coding genes.
Refined selection logic
Prior to v39.0, if a variant overlapped an RNA gene from the prioritized list, the RNA transcript was often chosen as the main_gene, even when a protein-coding gene had a more impactful variant.
Starting with v39.0"
Protein-coding genes with stronger effects now take priority over RNA genes.
RNA genes are still considered, but no longer override coding transcripts with higher significance.
This results in more more clinically meaningful main_gene selection.
Transcript prioritization v37.0, 38.0
Here is a list of ordered rules for transcript prioritization:
VEP transcripts are prioritized over EFF transcripts.
If the case is a virtual panel, prioritize transcripts from genes in the case gene list (but not for Boosted Genes type panels).
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.
De-prioritize biotype readthrough transcripts.
Prioritize based on impact in the following order: HIGH > MODERATE > LOW > MODIFIER.
Prioritize introns over UTR over upstream (Appendix 2: MODIFIER effects prioritization).
Prioritize organization canonical transcripts (Defined in Curate. Always applied, no settings needed).
Prioritize canonical transcripts (Based on Appris).
Prioritize transcripts from genes in the case gene list.
Prioritize gene without “-” in their Name.
Transcript prioritization before v37.0
Here is a list of ordered rules for transcript prioritization:
VEP transcripts are prioritized over EFF transcripts.
If the case is a virtual panel, prioritize transcripts from genes in the case gene list (but not for Boosted Genes type panels).
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.
De-prioritize biotype readthrough transcripts.
Prioritize based on impact in the following order: HIGH > MODERATE > LOW > MODIFIER.
Prioritize introns over UTR over upstream (Appendix 2: MODIFIER effects prioritization).
Prioritize organization canonical transcripts (Defined in Curate, this parameter has to be implemented upon request).
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
The prioritized RNA gene list has been updated in v39.0 to include newly supported genes and remove those with limited pathogenic evidence.
Added RNA genes (v39.0): CHASERR, MIR17HG, RNU2-2, RNU5A-1, RNU5B-1, TRU-TCA1-1, SNORA31
Removed RNA genes (v39.0): HELLPAR, LINC00237, GNAS-AS1, MEG3, LINC00299
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
Warning: If Curate preferred transcripts are enabled, transcript selection may differ from previous versions. This may change the displayed main gene/effect for some variants.
Tip: To ensure consistent results across teams, confirm whether Curate transcript prioritization is enabled for your organization.
Last updated
Was this helpful?