brentp / geneimpacts Goto Github PK

we have HIGH, MEDIUM and LOW, within those, we will order by priority and use

http://uswest.ensembl.org/info/genome/variation/predicted_data.html#consequences

as an ordering.

Your module asked me to report the following lines. Is there an explanation to why the severity for these particular consequences create issues?

Also, how does your program treat comma separated multiline CSQ?

WARNING: unknown severity for 'G|3_prime_UTR_variant|MODIFIER|PINK1|ENSG00000158828|Transcript|ENST00000321556|protein_coding|8/8||||2021|||||||1||HGNC|14581|YES' with effect 'G' Please report this on github with the effect-string above WARNING: unknown severity for 'G|downstream_gene_variant|MODIFIER|DDOST|ENSG00000244038|Transcript|ENST00000375048|protein_coding|||||||||||905|-1||HGNC|2728|YES' with effect 'G' Please report this on github with the effect-string above WARNING: unknown severity for 'G|non_coding_transcript_exon_variant|MODIFIER|PINK1|ENSG00000158828|Transcript|ENST00000400490|processed_transcript|4/4||||1020|||||||1||HGNC|14581|' with effect 'G' Please report this on github with the effect-string above WARNING: unknown severity for 'G|downstream_gene_variant|MODIFIER|DDOST|ENSG00000244038|Transcript|ENST00000415136|protein_coding|||||||||||1182|-1||HGNC|2728|' with effect 'G' Please report this on github with the effect-string above WARNING: unknown severity for 'G|non_coding_transcript_exon_variant|MODIFIER|PINK1-AS|ENSG00000117242|Transcript|ENST00000451424|retained_intron|1/3||||1322|||||||-1||HGNC|38872|YES' with effect 'G' Please report this on github with the effect-string above WARNING: unknown severity for 'G|downstream_gene_variant|MODIFIER|DDOST|ENSG00000244038|Transcript|ENST00000464364|protein_coding|||||||||||4568|-1|cds_end_NF|HGNC|2728|' with effect 'G' Please report this on github with the effect-string above WARNING: unknown severity for 'G|downstream_gene_variant|MODIFIER|DDOST|ENSG00000244038|Transcript|ENST00000475210|processed_transcript|||||||||||1762|-1||HGNC|2728|' with effect 'G' Please report this on github with the effect-string above WARNING: unknown severity for 'G|non_coding_transcript_exon_variant|MODIFIER|PINK1|ENSG00000158828|Transcript|ENST00000492302|processed_transcript|5/5||||3377|||||||1||HGNC|14581|' with effect 'G' Please report this on github with the effect-string above WARNING: unknown severity for 'G|upstream_gene_variant|MODIFIER|AL391357.1|ENSG00000257033|Transcript|ENST00000535128|pseudogene|||||||||||158|-1||Clone_based_ensembl_gene||YES' with effect 'G' Please report this on github with the effect-string above WARNING: unknown severity for 'G|downstream_gene_variant|MODIFIER|DDOST|ENSG00000244038|Transcript|ENST00000602624|protein_coding|||||||||||905|-1||HGNC|2728|' with effect 'G' Please report this on github with the effect-string above

The default annotations provided by snpEff include NextProt and Motif consequences. geneimpacts exits with a KeyError (in geneimpacts/effect.py line 557, for example: KeyError: 'NEXT_PROT[disulfide_bond]' when executing the line sevs = [IMPACT_SEVERITY[csq] for csq in self.consequences]) when these are present, since there is no entry in self.consequences for these effects.

using VEP v105.0:
WARNING: unknown severity for 'T|splice_donor_region_variant&intron_variant|LOW|SAMD11|ENSG00000187634|Transcript|ENST00000342066|protein_coding||1/13|ENST00000342066.8:c.-21+3G>T|||||||1||1||SNV|HGNC|HGNC:28706||||5||CCDS2.2|ENSP00000342313|Q96NU1-3|Ensembl|||||||||||||||' with effect 'splice_donor_region_variant'

When using Ensembl VEP version 105 we get following vcf2db warnings:

[2022-07-07T10:19Z] WARNING: unknown severity for 'C|splice_donor_region_variant&intron_variant|LOW|NOC2L|ENSG00000188976|Transcript|ENST00000327044|protein_coding||8/18|ENST00000327044.7:c.888+4C>G|||||||rs13303056|1||-1||SNV|HGNC|HGNC:24517|YES|NM_015658.4||1|P1|CCDS3.1|ENSP00000317992|Q9Y3T9.182||UPI000041820C|||Ensembl||G|G|||||||chr1:g.953778G>C||0.829|0.9135|0.9365|0.9523|0.9172|0.8238|0.9333|0.9321|0.8235|0.9508|0.9351|0.9215|0.9599|0.9413|0.9357|0.9192|0.9599|gnomAD_FIN||||||||||NOC2L:K296int|1&1&4||NOC2L&NM_015658.3&c.888+4C>G|||||INTRON_END:953781&DONOR_ESS:4&DONOR_ISS:4&EXON_END:953892&DONOR_GERP_DIFF:NA&DONOR_ESE:45&MUTANT_DONOR_MES:8.46099459345687&EXON_START:953782&DONOR_ISE:20&BRANCHPOINT_DISTANCE:NA&INTRON_START:953289&DONOR_MES_DIFF:-0.0169218360392236|8.461|-0.017|8.444|splice_donor_region_variant' with effect 'splice_donor_region_variant'
[2022-07-07T10:19Z] Please report this on github with the effect-string above

[2022-07-07T08:07Z] WARNING: unknown severity for 'A|splice_polypyrimidine_tract_variant&intron_variant|LOW|PKD1|ENSG00000008710|Transcript|ENST00000262304|protein_coding||12/45|ENST00000262304.9:c.2986-15C>T|||||||rs2855349&COSV51915841|1||-1||SNV|HGNC|HGNC:9008|YES|NM_001009944.3||1|A2|CCDS32369.1|ENSP00000262304|P98161.246||UPI00001B0454|P98161-1||Ensembl||G|G||1|||||chr16:g.2112978G>A|0.1016|0.0212|0.0346|0.2589|0.0199|0.18|0.01959|0.01593|0.05527|0.02214|0.04355|0.01434|0.2355|0.006574|0.01323|0.03884|0.168|0.2589|EAS|benign|0&1|1&1|25741868||||||-15|-38|-47|-32|0.00|0.00|0.00|0.00|PKD1||||ACCEPTOR_ESS:4&MUTANT_ACCEPTOR_MES:9.72629935165179&INTRON_START:2112964&EXON_START:2112788&EXON_END:2112963&ACCEPTOR_ESE:34&ACCEPTOR_GERP_DIFF:NA&INTRON_END:2113160&ACCEPTOR_MES_DIFF:0.0275745470020006&ACCEPTOR_ISS:11&BRANCHPOINT_DISTANCE:20&ACCEPTOR_ISE:9|9.726|0.028|9.754|splice_polypyrimidine_tract_variant' with effect 'splice_polypyrimidine_tract_variant'
[2022-07-07T08:07Z] Please report this on github with the effect-string above

We use geneimpacts v0.3.7. Could this been fixed?

Thank you in advance

In the interest of reducing false negatives.

currently, some '+' events are hard-coded into the order. I should split on '+' and keep the highest priority.

Hi @brentp !

Could you please create a new release of geneimpacts?
Otherwise the change #16
is not propagated to bioconda/bcbio and ensembl_gene_id is empty in gemini.db
after bcbio upgrade.

Thanks!
Sergey