[0] : FunMotifs BED file
[1]+ : List of columns to include within the output (e.g. fscore, skin, contactingdomain)
gene2phenotype | An Ensembl VEP plugin that uses G2P (www.ebi.ac.uk/gene2phenotype) allelic requirements to assess variants in genes
for potential phenotype involvement. more The plugin has multiple configuration options, though minimally requires only
the CSV file of G2P data.
This Plugin is available for GRCh38 and GRCh37. For further information see:
Thormann A, Halachev M, McLaren W, et al. Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP.
Nature Communications. 2019 May;10(1):2373. doi:10.1038/s41467-019-10016-3. PMID: 31147538; PMCID: PMC6542828. To improve performance, we recommend running VEP with multiple forks using the --fork <n> option where <n>
is the number of parallel processes. For the G2P plugin we recommend using 4 forks (--fork 4). G2P data file:
- To run the plugin it is necessary to provide a data file either downloaded from G2P or PanelApp.
- The G2P file can be downloaded from:
+ To run the plugin it is necessary to provide an uncompressed data file downloaded from G2P, PanelApp or GenCC.
+ G2P files can be downloaded from:
Options are passed to the plugin as key=value pairs, (defaults in parentheses): | Argument | Description |
|---|
-file | Path to G2P data file. The file needs to be uncompressed.
- | variant_include_list | A list of variants to include even if variants do not pass allele frequency filtering. The include list needs to be a sorted, bgzipped and
+ | file | Path to the input data file. Supported formats are csv (G2P, GenCC) and tsv (PanelApp). The file needs to be uncompressed. | variant_include_list | A list of variants to include even if variants do not pass allele frequency filtering. The include list needs to be a sorted, bgzipped and
tabixed VCF file. | af_monoallelic | maximum allele frequency for inclusion for monoallelic genes (0.0001)
| af_biallelic | maximum allele frequency for inclusion for biallelic genes (0.005)
| confidence_levels | Confidence levels include: definitive, strong, moderate, limited Former confidence terms are still supported: confirmed, probable, possible, both RD and IF.
Separate multiple values with &.
https://www.ebi.ac.uk/gene2phenotype/terminology
- Default levels are confirmed and probable. | all_confidence_levels | Set to 1 to include all confidence levels Setting the value to 1 will overwrite any confidence levels provided with the
- confidence_levels option. | af_from_vcf | set value to 1 to include allele frequencies from VCF file. Specifiy the list of reference populations to include with --af_from_vcf_keys | af_from_vcf_keys | VCF collections used for annotating variant alleles with observed allele frequencies. Allele frequencies are retrieved from VCF files. If
+ Default levels are definitive, strong and moderate (and former terms: confirmed, probable). | all_confidence_levels | Set to 1 to include all confidence levels. Setting the value to 1 will overwrite any confidence levels provided with the
+ confidence_levels option.
+ Not recommended for diagnostic reporting. | af_from_vcf | set value to 1 to include allele frequencies from VCF file. Specifiy the list of reference populations to include with --af_from_vcf_keys | af_from_vcf_keys | VCF collections used for annotating variant alleles with observed allele frequencies. Allele frequencies are retrieved from VCF files. If
af_from_vcf is set to 1 but no VCF collections are specified with --af_from_vcf_keys
all available VCF collections are included.
- Available VCF collections: topmed, uk10k, gnomADe, gnomADe_r2.1.1, gnomADg, gnomADg_v3.1.2, gnomADev4.1, gnomADgv4.1.
+ Available VCF collections: topmed, uk10k, gnomADe, gnomADe_r2.1.1, gnomADg, gnomADg_v3.1.2, gnomADe_v4.1, gnomADg_v4.1.
Separate multiple values with &.
VCF collections contain the following populations:
-- topmed - TOPMed (available for GRCh37 and GRCh38).
- uk10k - ALSPAC, TWINSUK (available for GRCh37 and GRCh38).
- gnomADe & 'gnomADe_r2.1.1 & gnomADev4.1 - gnomADe:AFR, gnomADe:ALL, gnomADe:AMR, gnomADe:ASJ, gnomADe:EAS, gnomADe:FIN, gnomADe:NFE, gnomADe:OTH, gnomADe:SAS (for GRCh37 and GRCh38 respectively).
- gnomADg & gnomADg_v3.1.2 & gnomADgv4.1 - gnomADg:AFR, gnomADg:ALL, gnomADg:AMR, gnomADg:ASJ, gnomADg:EAS, gnomADg:FIN, gnomADg:NFE, gnomADg:OTH (for GRCh37 and GRCh38 respectively). Need to use af_from_vcf parameter to use this option.
only_vcf_freq
| set to 1 to only use frequency from vcf files, can only be set if af_from_vcf is set. N/B - frequency information may be lost if this option is used | default_af | default frequency of the input variant if no frequency data is found (0). This determines whether such variants are included;
- the value of 0 forces variants with no frequency data to be
- included as this is considered equivalent to having a frequency
- of 0. Set to 1 (or any value higher than af) to exclude them. | types | SO consequence types to include. Separate multiple values with & (splice_donor_variant, splice_acceptor_variant, stop_gained,
+- topmed - TOPMed (available for GRCh37 and GRCh38).
- uk10k - ALSPAC, TWINSUK (available for GRCh37 and GRCh38).
- gnomADe & gnomADe_r2.1.1 & gnomADe_v4.1 - gnomADe:AFR, gnomADe:ALL, gnomADe:AMR, gnomADe:ASJ, gnomADe:EAS, gnomADe:FIN, gnomADe:NFE, gnomADe:OTH, gnomADe:SAS (for GRCh37 and GRCh38 respectively).
- gnomADg & gnomADg_v3.1.2 & gnomADg_v4.1 - gnomADg:AFR, gnomADg:ALL, gnomADg:AMR, gnomADg:ASJ, gnomADg:EAS, gnomADg:FIN, gnomADg:NFE, gnomADg:OTH (for GRCh37 and GRCh38 respectively). Need to use af_from_vcf parameter to use this option.
only_vcf_freq
| set to 1 to only use frequency from vcf files, can only be set if af_from_vcf is set. N/B - frequency information may be lost if this option is used | types | Ensembl VEP SO consequence terms to include. Separate multiple values with &. This option replaces the default list. By default, the plugin uses:
+ splice_donor_variant, splice_acceptor_variant, stop_gained,
+ splice_donor_region_variant, splice_donor_5th_base_variant,
+ splice_region_variant, splice_polypyrimidine_tract_variant,
frameshift_variant, stop_lost, initiator_codon_variant,
inframe_insertion, inframe_deletion,missense_variant,
coding_sequence_variant, start_lost,transcript_ablation,
- transcript_amplification, protein_altering_variant) | log_dir | write stats to log files in log_dir
+ transcript_amplification, protein_altering_variant | add_types | Ensembl VEP SO consequence terms to append to the default types list. Separate multiple values with &.
+ This option cannot be used together with types. | log_dir | write stats to log files in log_dir
| txt_report | write all G2P complete genes and attributes to txt file
| html_report | write all G2P complete genes and attributes to html file
- | filter_by_gene_symbol | set to 1 if filter by gene symbol. Do not set if filtering by HGNC_id.
- This option is set to 1 when using PanelApp files. | filter_consequence_match | to only report variants where the VEP predicted consequence matches the G2P variant consequence (GenCC term). Accepted values are:
-- broad: includes 'almost always', probable and possible matches
- strict: includes 'almost always' and probable matches More details in https://europepmc.org/article/MED/37982373
- See here for the list of supported variant consequences in G2P: https://www.ebi.ac.uk/gene2phenotype/about/terminology#variant-consequence-section
flag_consequence_match
| flag if the VEP predicted consequence matches the G2P variant consequence (GenCC term). Accepted values are:
-- broad: includes 'almost always', probable and possible matches
- strict: includes 'almost always' and probable matches More details in https://europepmc.org/article/MED/37982373
only_mane
| set to 1 to ignore transcripts that are not MANE N/B - Information may be lost if this option is used. | include_disease | set to 1 to report the G2P disease name in the VEP output. The disease name is not included in the G2P report files. |
|
|
|
|
+ filter_by_gene_symbol | set to 1 if filtering by gene symbol. Do not set if filtering by HGNC_id.
+ This option is set to 1 automatically when using PanelApp files. | gencc_submitter | Required when using a GenCC input file. Filters the GenCC file to rows whose submitted_as_submitter_name
+ matches this value.
+ Matching is case-insensitive.
+ Empty submitter names are not supported. | filter_consequence_match | to only report variants where the VEP predicted consequence matches the G2P variant consequence term (GenCC term).
+ Accepted values are:
+- broad: includes almost always, probable and possible matches
- strict: includes almost always and probable matches This option is only supported with G2P input files.
+
+ More details in https://europepmc.org/article/MED/37982373
+ See here for the list of supported variant consequences in G2P:
+ https://www.ebi.ac.uk/gene2phenotype/about/terminology#variant-consequence-section
flag_consequence_match
| flag if the VEP predicted consequence matches the G2P variant consequence term (GenCC term).
+ Accepted values are:
+- broad: includes 'almost always', probable and possible matches
- strict: includes 'almost always' and probable matches This option is only supported with G2P input files.
+ More details in https://europepmc.org/article/MED/37982373
only_mane
| set to 1 to ignore transcripts that are not MANE N/B - Information may be lost if this option is used. | include_disease | set to 1 to report the disease name from the input file in the VEP output. The disease name is not included in the G2P report files. |
For more information - https://www.ebi.ac.uk/gene2phenotype/variant-filtering Example:
--plugin G2P,file=G2P.csv,af_monoallelic=0.05,types=stop_gained&frameshift_variant
--plugin G2P,file=G2P.csv,af_monoallelic=0.05,af_from_vcf=1
|
| |