annovar.openbioinformatics.orgANNOVAR Documentation
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Toggle navigation ANNOVAR User Guide Download ANNOVAR Quick Start-Up Guide Prepare Input Files Gene-based Annotation Region-based Annotation Filter-based Annotation Misc Accessory Programs FAQ What is New Version History Credit How to Contribute Articles VCF Processing Guide Assigning dbSNP Identifiers wANNOVAR Tutorial Search Previous Next Edit on GitHub Reference ANNOVAR is an efficient software tool to utilize update-to-date information to functionally annotate genetic variants detected from diverse genomes (including human genome hg18, hg19, hg38, as well as mouse, worm, fly, yeast and many others). Given a list of variants with chromosome, start position, end position, reference nucleotide and observed nucleotides, ANNOVAR can perform: Gene-based annotation : identify whether SNPs or CNVs cause protein coding changes and the amino acids that are affected. Users can flexibly use RefSeq genes, UCSC genes, ENSEMBL genes, GENCODE genes, AceView genes, or many other gene definition systems. Region-based annotation : identify variants in specific genomic regions, for example, conserved regions among 44 species, predicted transcription factor binding sites, segmental duplication regions, GWAS hits, database of genomic variants, DNAse I hypersensitivity sites, ENCODE H3K4Me1/H3K4Me3/H3K27Ac/CTCF sites, ChIP-Seq peaks, RNA-Seq peaks, or many other annotations on genomic intervals. Filter-based annotation : identify variants that are documented in specific databases, for example, whether a variant is reported in dbSNP, what is the allele frequency in the 1000 Genome Project, NHLBI-ESP 6500 exomes or Exome Aggregation Consortium (ExAC) or Genome Aggregation Database (gnomAD), calculate the SIFT/PolyPhen/LRT/MutationTaster/MutationAssessor/FATHMM/MetaSVM/MetaLR scores, find intergenic variants with GERP++ score<2 or CADD>10, or many other annotations on specific mutations. Other functionalities : Retrieve the nucleotide sequence in any user-specific genomic positions in batch, identify a candidate gene list for Mendelian diseases from exome data, and other utilities. Please click the menu items to navigate through this website. If you have questions, comments and bug reports, please post them in the Disqus comment form in this website (if you do not receive a reply within 7 days, post it again, since sometimes I miss the Disqus notification email or I click the notification email but cannot find the question if a page has too many Disqus posts) or you can just email me directly kaichop gmail.com. Thank you very much for your help and support! 2020Jun08: The gene annotation for SARS-CoV-2 are updated at the annotation files avGene.txt.gz and avGeneMrna.fa.gz , so that nsp1-nsp16 can all be annotated now, in addition to ORF1ab and ORF1a. Additionally, I made very minor change to increase compatibility of ANNOVAR in Windows Powershell. 2020Apr28: A number of ANNOVAR users asked how to analyze mutations in SARS-CoV-2. In general this can be done following the procedure described in the "Gene-based Annotation" page for expert users, but it requires some tweaking of the GFF files provided by NCBI's gene annotation (because NCBI's file treat ORF1a and ORF1ab as two isoforms of a single gene named ORF1ab, and because there is a ribosome slippage event in ORF1ab that creates a scenraio where the same base can belong to two adjacent codons). To make things easier for ANNOVAR users, I now manually created the gene annotation called avGene and provide the annotation files avGene.txt.gz and avGeneMrna.fa.gz . Please note that (1) to be consistent with UCSC Genome Browser's reference FASTA , you must use NC_045512v2 rather than NC_045512.2 as the reference chromosome name in your input file to ANNOVAR; (2) I use the known names of four structural proteins as spike glycoprotein (S), matrix protein (M), envelope protein (E), and nucleocapsid protein (N), rather than ORF2, ORF4, ORF5 and ORF9; (3) I feel it is more appropriate to call the two overlapping genes/isoforms and protein products as ORF1ab and ORF1a rather than calling them both as ORF1ab, and treat the 16 non-structural proteins (NSPs) as secondary post-translation mature products of ORF1ab/ORF1a protein (In June update described above, this scenario is now handled). To give an example, you can use NC_045512v2 29095 29095 C T as the input file to ANNOVAR command table_annovar.pl -buildver NC_045512v2 mut1.avinput sarscov2db/ -protocol avGene -operation g , and see the annotation as "N:YP_009724397.2:exon1:c.C822C:p.F274F" in the output. Next try NC_045512v2 26144 26144 G T and see what you get. Finally, try NC_045512v2 28144 28144 T C as the input. Note that these mutations were reported in a recently published paper but there are some mistakes in their strand assignment and annotation. 2020Apr01: Clinvar annotation (version 20200316) is available in ANNOVAR now. 2019Dec03: ANNOVAR download consistently exceeds >10TB/month over the past two months and the cost for hosting it at AWS is absurdly high (unfortunately currently no grant funding is available to support ANNOVAR). During the next a few days, I will migrate ANNOVAR out of AWS to a new CDN provider and test it over the next two months. Expect some connection issues when you do -downdb depending on your geographical locations over the next a few days. (Update 2019Dec06: Migration is completed successfully, please report issues if you encounter any). 2019Nov27: A slight change was made to coding_change.pl to fix the 'argument G is not numeric in numeric gt (>)' bug for startloss mutations, and you can download the updated file here . Please report additioanl bugs on the 2019Oct24 version to me if you find any. 2019Nov04: gnomAD version 3.0 on hg38 coordinate is available in ANNOVAR (use gnomad30_genome to download). Only variants from whole-genome (but not whole-exome) sequencing are available. 2019Nov01: gene4denovo annotation database with 580K de novo mutations for hg19/hg38 are available in ANNOVAR (use hg19_gene4denovo201907 and hg38_gene4denovo201907 keywords to download). Read here for more information. 2019Oct24: New ANNOVAR version (20191024) is available. It should be considered as a release candidate for public testing. Please report bugs and comments and thank you in advance!!! Major changes: allow refGeneWithVer as a valid gene annotation when using -downdb argument in annotate_variation.pl; add -intronhgvs argument to print out HGVS notations for intronic variants; add startloss and startgain as functional consequences that affects the first ATG codon; add -nofirstcodondel to table_annovar by default to enable calculation of amino acid changes for certain variants previously annotated as 'wholegene'; minor adjustment on nonframeshift vs startloss vs stopgain for certain variants with multiple valid notations; changed p. notation for block substitution that does not cause protein change; changed table_annovar so that ExAC and gnomAD are treated as float fields in VCF annotation; allow genericdb for region annotation; allow chromosome name to contain . or - for certain species; the -polish argument is ON by default in table_annovar.pl; table_annovar.pl can generate column headers such as Otherinfo, Otherinfo2, Otherinfo3, etc; fixed a bug of cdot notation for block substitutions that cover 5UTR and start codon 2019Sep29: All ANNOVAR databases are transferred to AWS S3, including large files. The refGene, refGeneWithVer, knownGene and ensGene (same as GencodeBasicV31) for hg18/hg19/hg38 are updated to the latest version. 2019Jun17: All ANNOVAR databases are transferred to AWS S3, except a few large (>100GB) files. Please report any problem that you see. June 16 2019: The hosting provider deleted all ANNOVAR files and I am in the process of finding alternative solutions. Hopefully ANNOVAR database will be online again early next week. May 2019: We are in the process of moving ANNOVAR server to a different hosting vendor. There is n...
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