CADD (Combined Annotation Dependent Depletion) is a tool for scoring the deleteriousness of single nucleotide variants as well as insertion/deletions variants in the human genome. Currently, it supports the builds: GRCh37/hg19 and GRCh38/hg38.

References:

• Martin Kircher, Daniela M Witten, Preti Jain, Brian J O'Roak, Gregory M Cooper & Jay Shendure
  A general framework for estimating the relative pathogenicity of human genetic variants.
  Nature Genetics 2014 Feb 2. doi: 10.1038/ng.2892.
• Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher M.
  CADD: predicting the deleteriousness of variants throughout the human genome.
  Nucleic Acids Res. 2018 Oct 29. doi: 10.1093/nar/gky1016.
  

• CADD Github page

• Module Name: CADD (see the modules page for more information)
• Unusual environment variables set
  • CADD_HOME  CADD installation directory
  • CADD_BIN       CADD executable directory
  • CADD_DATA   CADD data directory

Allocate an interactive session and run the program. Sample session:

[user@biowulf]$ sinteractive 
[user@cn4206 ~]$ module load cadd 
[+] Loading snakemake  6.5.3
[+] Loading CADD 1.6.post1 on cn4206
[user@cn4206 ~]$ which CADD
/usr/local/apps/CADD/1.6.post1/bin/CADD
user@cn4206 ~]$ CADD -h
CADD [-o ] [-g ] [-v ] [-a]   -- CADD version 1.6

where:
    -h  show this help text
    -o  out tsv.gz file (generated from input file name if not set)
    -g  genome build (supported are GRCh37 and GRCh38 [default: GRCh38])
    -v  CADD version (only v1.6 possible with this set of scripts [default: v1.6])
    -a  include annotation in output
        input vcf of vcf.gz file (required)
    -q  print basic information about snakemake run
    -p  print full information about the snakemake run
    -c  number of cores that snakemake is allowed to use [default: 1]
[user@cn4206 ~]$ CADD -o my_out.tsv.gz -g GRCh38 $CADD_TEST/input.vcf
CADD-v1.6 (c) University of Washington, Hudson-Alpha Institute for Biotechnology and Berlin Institute of Health 2013-2020. All rights reserved.
OUTFILE=my_out.tsv.gz
Running snakemake pipeline:
snakemake /tmp/tmp.jfNNBZaoNk/input.tsv.gz --use-conda --conda-prefix /vf/db/CADD/1.6.post1/envs --cores 1
--configfile /vf/db/CADD/1.6.post1/config/config_GRCh38_v1.6_noanno.yml --snakefile /vf/db/CADD/1.6.post1/Snakefile -q
Job stats:
job           count    min threads    max threads
----------  -------  -------------  -------------
annotation        1              1              1
imputation        1              1              1
join              1              1              1
prepare           1              1              1
prescore          1              1              1
score             1              1              1
total             6              1              1

Opening /vf/db/CADD/1.6.post1/data/prescored/GRCh38_v1.6/no_anno/gnomad.genomes.r3.0.indel.tsv.gz...
Opening /vf/db/CADD/1.6.post1/data/prescored/GRCh38_v1.6/no_anno/whole_genome_SNVs.tsv.gz...
Possible precedence issue with control flow operator at /vf/db/CADD/1.6.post1/envs/e507b9d6fe0a5d0ae12148a5d819bc0e/lib/site_perl/5.26.2/Bio/DB/IndexedBase.pm line 805.

CADD scored variants written to file: my_out.tsv.gz

[user@cn4206 ~]$ CADD -o my_out.tsv.gz -g GRCh38 $CADD_TEST/input.vcf
CADD-v1.6 (c) University of Washington, Hudson-Alpha Institute for Biotechnology and Berlin Institute of Health 2013-2020. All rights reserved.
Running snakemake pipeline:
snakemake /tmp/tmp.scK9I9hCpe/input.tsv.gz --use-conda --conda-prefix /vf/db/CADD/1.6.post1/envs --cores 1
--configfile /vf/db/CADD/1.6.post1/config/config_GRCh37_v1.6_noanno.yml --snakefile /vf/db/CADD/1.6.post1/Snakefile -q
Job stats:
job           count    min threads    max threads
----------  -------  -------------  -------------
annotation        1              1              1
imputation        1              1              1
join              1              1              1
prepare           1              1              1
prescore          1              1              1
score             1              1              1
total             6              1              1

Opening /vf/db/CADD/1.6.post1/data/prescored/GRCh37_v1.6/no_anno/InDels.tsv.gz...
Opening /vf/db/CADD/1.6.post1/data/prescored/GRCh37_v1.6/no_anno/whole_genome_SNVs.tsv.gz...
Possible precedence issue with control flow operator at /vf/db/CADD/1.6.post1/envs/e507b9d6fe0a5d0ae12148a5d819bc0e/lib/site_perl/5.26.2/Bio/DB/IndexedBase.pm line 805.

CADD scored variants written to file: my_out.tsv.gz

[user@cn4206 ~]$ exit
salloc.exe: Relinquishing job allocation 46116226
[user@biowulf ~]$