Ensembl Variant Effect Predictor (VEP) issue during execution

Question

I got this error during execution, pls guide me.

vep --cache -i xxxx.vcf -o xxxxx_new.vcf

Possible precedence issue with control flow operator at /software/xxxx_pkgs/envs/ensemble-vep/lib/site_perl/5.26.2/Bio/DB/IndexedBase.pm line 805.
DBI connect('host=ensembldb.ensembl.org;port=3306','anonymous',...) failed: Can't connect to MySQL server on 'ensembldb.ensembl.org' (110) at /software/xxxx_pkgs/envs/ensemble-vep/share/ensembl-vep-88.9-1/Bio/EnsEMBL/Registry.pm line 1771.

-------------------- EXCEPTION --------------------
MSG: Cannot connect to the Ensembl MySQL server at ensembldb.ensembl.org:3306; check your settings & DBI error message: Can't connect to MySQL server on 'ensembldb.ensembl.org' (110)
STACK Bio::EnsEMBL::Registry::load_registry_from_db /software/xxxx_pkgs/envs/ensemble-vep/share/ensembl-vep-88.9-1/Bio/EnsEMBL/Registry.pm:1771
STACK Bio::EnsEMBL::VEP::BaseVEP::registry /software/xxxx_pkgs/envs/ensemble-vep/share/ensembl-vep-88.9-1/modules/Bio/EnsEMBL/VEP/BaseVEP.pm:163
STACK Bio::EnsEMBL::VEP::BaseRunner::setup_db_connection /software/xxxx_pkgs/envs/ensemble-vep/share/ensembl-vep-88.9-1/modules/Bio/EnsEMBL/VEP/BaseRunner.pm:80
STACK Bio::EnsEMBL::VEP::Runner::init /software/xxxx_pkgs/envs/ensemble-vep/share/ensembl-vep-88.9-1/modules/Bio/EnsEMBL/VEP/Runner.pm:72
STACK Bio::EnsEMBL::VEP::Runner::run /software/xxxx_pkgs/envs/ensemble-vep/share/ensembl-vep-88.9-1/modules/Bio/EnsEMBL/VEP/Runner.pm:111
STACK toplevel /software//envs/ensemble-vep/bin/vep:209
Ensembl API version = 88
```

Answer 1

You might prefer to run VEP in offline mode:

Using --cache (without --offline) uses the local cache on disk to fetch most annotations, but allows database connections for some features (see cache limitations)

If you need HGVS names in your output, you'll also need to supply a FASTA file using --fasta:

--offline

Enable offline mode. No database connections will be made, and a cache file or GFF/GTF file is required for annotation. Add --refseq to use the refseq cache (if installed). Not used by default.

--fasta [file|dir]

Specify a FASTA file or a directory containing FASTA files to use to look up reference sequence. The first time you run VEP with this parameter an index will be built which can take a few minutes. This is required if fetching HGVS annotations (--hgvs) or checking reference sequences (--check_ref) in offline mode (--offline), and optional with some performance increase in cache mode (--cache). See documentation for more details. Not used by default.