> For the complete documentation index, see [llms.txt](https://help.bioinsight.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.bioinsight.illumina.com/annotation/v4.0/core-functionality/transcript-consequence-impacts.md). # Transcript Consequence Impact ### Overview DRAGEN Annotation provides transcript consequence impacts from [SnpEff](https://pcingola.github.io/SnpEff). Following definitions are used for the impact ratings as obtained from [SnpEff](https://github.com/pcingola/SnpEff/blob/master/src/docs/se_inputoutput.md#impact-prediction). | Impact | Definition | | -------- | -------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | high | The variant is assumed to have high (disruptive) impact in the protein, probably causing protein truncation, loss of function or triggering nonsense mediated decay. | | moderate | A non-disruptive variant that might change protein effectiveness. | | low | Assumed to be mostly harmless or unlikely to change protein behavior. | | modifier | Usually non-coding variants or variants affecting non-coding genes, where predictions are difficult or there is no evidence of impact. | ### Sources Not all consequences are rated by SnpEff, therefore DRAGEN Annotation combines the ratings from SnpEff with those from VEP. 1. SnpEff [Documentation](https://pcingola.github.io/SnpEff/se_inputoutput/) and [Codebase](https://github.com/pcingola/SnpEff/blob/001b947893b616e3af082e6c565e253eef59db98/src/main/java/org/snpeff/snpEffect/EffectType.java#L54) 2. VEP [Documentation](https://useast.ensembl.org/info/genome/variation/prediction/predicted_data.html) ### Consequence Impacts Following table gives the combined rating for all consequences recognized by DRAGEN Annotation. | Consequence | SnpEff Impact | VEP Impact | DRAGEN Annotation Impact | Comment | | -------------------------------------- | ------------- | ---------- | ------------------------ | --------------------------------------- | | bidirectional\_gene\_fusion | high | | high | SnpEff | | coding\_sequence\_variant | low, modifier | modifier | modifier | Based on CDS | | copy\_number\_change | | | modifier | | | copy\_number\_decrease | | | modifier | | | copy\_number\_increase | | | modifier | | | downstream\_gene\_variant | modifier | modifier | modifier | SnpEff + VEP | | feature\_elongation | modifier | high | high | VEP | | feature\_truncation | | high | high | VEP | | five\_prime\_duplicated\_transcript | | | modifier | | | five\_prime\_UTR\_variant | modifier | modifier | modifier | SnpEff + VEP | | frameshift\_variant | high | high | high | SnpEff + VEP | | gene\_fusion | high | | high | SnpEff | | incomplete\_terminal\_codon\_variant | | low | low | VEP | | inframe\_deletion | moderate | moderate | moderate | SnpEff + VEP | | inframe\_insertion | moderate | moderate | moderate | SnpEff + VEP | | intron\_variant | modifier | modifier | modifier | SnpEff + VEP | | mature\_miRNA\_variant | | modifier | modifier | VEP | | missense\_variant | moderate | moderate | moderate | SnpEff + VEP | | NMD\_transcript\_variant | | modifier | modifier | VEP | | non\_coding\_transcript\_exon\_variant | modifier | modifier | modifier | SnpEff + VEP | | non\_coding\_transcript\_variant | modifier | modifier | modifier | SnpEff + VEP | | protein\_altering\_variant | | moderate | moderate | VEP | | regulatory\_region\_ablation | | modifier | modifier | VEP | | regulatory\_region\_amplification | | modifier | modifier | VEP | | regulatory\_region\_variant | modifier | modifier | modifier | SnpEff + VEP | | TFBS\_ablation | | modifier | | VEP | | TFBS\_amplification | | modifier | | VEP | | TF\_binding\_site\_variant | | modifier | | VEP | | short\_tandem\_repeat\_change | | | modifier | | | short\_tandem\_repeat\_contraction | | | modifier | | | short\_tandem\_repeat\_expansion | | | modifier | | | splice\_acceptor\_variant | high | high | high | SnpEff + VEP | | splice\_donor\_variant | high | high | high | SnpEff + VEP | | splice\_donor\_region\_variant | | low | | | | splice\_donor\_5th\_base\_variant | | low | | | | splice\_polypyrimidine\_tract\_variant | | low | | | | splice\_region\_variant | moderate, low | low | low | Based on SPLICE\_SITE\_REGION in SnpEff | | start\_lost | high | high | high | SnpEff + VEP | | start\_retained\_variant | low | low | low | SnpEff + VEP | | stop\_gained | high | high | high | SnpEff + VEP | | stop\_lost | high | high | high | SnpEff + VEP | | stop\_retained\_variant | low | low | low | SnpEff + VEP | | synonymous\_variant | low | low | low | SnpEff + VEP | | three\_prime\_duplicated\_transcript | | | modifier | | | three\_prime\_UTR\_variant | modifier | modifier | modifier | SnpEff + VEP | | transcript\_ablation | high | high | high | SnpEff + VEP | | transcript\_amplification | | high | high | VEP | | transcript\_variant | modifier | | modifier | SnpEff | | unidirectional\_gene\_fusion | high | | high | SnpEff | | upstream\_gene\_variant | modifier | modifier | modifier | SnpEff + VEP | {% hint style="info" %} **Note:** 1. For transcripts with multiple consequences, the most severe impact rating is chosen. 2. In case of consequences that do not have any impact rating from SnpEff or VEP, DRAGEN Annotation provides `modifier`. {% endhint %} #### Known Issues {% hint style="warning" %} **Known Issues** The consequence `splice_polypyrimidine_tract_variant`, is rated as `low` by VEP. However, this consequence is not annotated by DRAGEN Annotation, therefore the impact will also not be provided. {% endhint %} ### Example Transcript The key `impact` for each transcript gives the impact rating for the `consequence`. ```json { "variants": [ { "vid": "1-1623412-T-C", "chromosome": "1", "begin": 1623412, "end": 1623412, "refAllele": "T", "altAllele": "C", "variantType": "SNV", "hgvsg": "NC_000001.11:g.1623412T>C", "transcripts": [ { "transcript": "ENST00000479659.5", "source": "Ensembl", "bioType": "lncRNA", "introns": "2/18", "geneId": "ENSG00000197530", "hgnc": "MIB2", "consequence": [ "intron_variant", "non_coding_transcript_variant" ], "impact": "modifier", "hgvsc": "ENST00000479659.5:n.288-19T>C" }, { "transcript": "ENST00000489635.5", "source": "VEP", "bioType": "mRNA", "codons": "aTg/aCg", "aminoAcids": "M/T", "cdnaPos": "269", "cdsPos": "134", "exons": "3/20", "proteinPos": "45", "geneId": "ENSG00000197530", "hgnc": "MIB2", "consequence": [ "missense_variant" ], "impact": "moderate", "hgvsc": "ENST00000489635.5:c.134T>C", "hgvsp": "ENSP00000426007.1:p.(Met45Thr)", "proteinId": "ENSP00000426007.1" } ] } ] } ``` --- # Agent Instructions This documentation is published with GitBook. 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