# Transcript prioritization logic

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 v37.0+

Here is a list of ordered rules for transcript prioritization:

{% stepper %}
{% step %}
VEP transcripts are prioritized over EFF transcripts.
{% endstep %}

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

{% step %}
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.
{% endstep %}

{% step %}
De-prioritize [biotype readthrough](https://www.ensembl.org/info/genome/genebuild/biotypes.html) transcripts.
{% endstep %}

{% step %}
Prioritize based on [impact](https://www.ensembl.org/info/genome/variation/prediction/predicted_data.html) in the following order: HIGH > MODERATE > LOW > MODIFIER.
{% endstep %}

{% step %}
Prioritize introns over UTR over upstream (Appendix 2: MODIFIER effects prioritization).
{% endstep %}

{% step %}
Prioritize organization canonical transcripts (Defined in Curate. Always applied, no settings needed).
{% endstep %}

{% step %}
Prioritize canonical transcripts (Based on [Appris](https://appris.bioinfo.cnio.es/#/)).
{% endstep %}

{% step %}
Prioritize transcripts from genes in the case gene list.
{% endstep %}

{% step %}
Prioritize gene without “-” in their Name.
{% endstep %}
{% endstepper %}

### Transcript prioritization before v37.0

Here is a list of ordered rules for transcript prioritization:

{% stepper %}
{% step %}
VEP transcripts are prioritized over EFF transcripts.
{% endstep %}

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

{% step %}
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.
{% endstep %}

{% step %}
De-prioritize [biotype readthrough](https://www.ensembl.org/info/genome/genebuild/biotypes.html) transcripts.
{% endstep %}

{% step %}
Prioritize based on [impact](https://www.ensembl.org/info/genome/variation/prediction/predicted_data.html) in the following order: HIGH > MODERATE > LOW > MODIFIER.
{% endstep %}

{% step %}
Prioritize introns over UTR over upstream (Appendix 2: MODIFIER effects prioritization).
{% endstep %}

{% step %}
Prioritize organization canonical transcripts (Defined in Curate, this parameter has to be implemented upon request).
{% endstep %}

{% step %}
Prioritize canonical transcripts (Based on [Appris](https://appris.bioinfo.cnio.es/#/)).
{% endstep %}
{% endstepper %}

### Appendixes

<details>

<summary>Appendix 1: List of RNA genes associated with disease</summary>

*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

</details>

<details>

<summary>Appendix 2: MODIFIER effects prioritization</summary>

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

</details>