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Spliceogenic variants, which alter mRNA splicing, may yield mature transcripts that encode non-functional protein products, an important predictor of Mendelian disease risk. However, most variant annotation tools do not adequately assess spliceogenicity outside the native splice site and thus the disease-causing potential of variants in other intronic and exonic regions is often overlooked. Here, we present a plugin for the Ensembl Variant Effect Predictor that packages MaxEntScan and extends its functionality to provide splice site predictions using a maximum entropy model. The plugin incorporates a sliding window algorithm to predict splice site loss or gain for any variant that overlaps a transcript feature. We also demonstrate the utility of the plugin by comparing our predictions to two mRNA splicing datasets containing several cancer-susceptibility genes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>Source code is freely available under the Apache License, Version 2.0: https:\/\/github.com\/Ensembl\/VEP_plugins.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/bty960","type":"journal-article","created":{"date-parts":[[2018,11,22]],"date-time":"2018-11-22T20:12:32Z","timestamp":1542917552000},"page":"2315-2317","source":"Crossref","is-referenced-by-count":80,"title":["A plugin for the Ensembl Variant Effect Predictor that uses MaxEntScan to predict variant spliceogenicity"],"prefix":"10.1093","volume":"35","author":[{"given":"Jannah","family":"Shamsani","sequence":"first","affiliation":[{"name":"Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane QLD, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen H","family":"Kazakoff","sequence":"additional","affiliation":[{"name":"Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane QLD, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina M","family":"Armean","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Will","family":"McLaren","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael T","family":"Parsons","sequence":"additional","affiliation":[{"name":"Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane QLD, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryony A","family":"Thompson","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne VIC, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracy A","family":"O\u2019Mara","sequence":"additional","affiliation":[{"name":"Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane QLD, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah E","family":"Hunt","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Waddell","sequence":"additional","affiliation":[{"name":"Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane QLD, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda B","family":"Spurdle","sequence":"additional","affiliation":[{"name":"Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane QLD, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,11,23]]},"reference":[{"key":"2023051612210442100_bty960-B1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/humu.10295","article-title":"Nonclassical splicing mutations in the coding and noncoding regions of the ATM Gene: maximum entropy estimates of splice junction strengths","volume":"23","author":"Eng","year":"2004","journal-title":"Hum. 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Cancer Res"},{"key":"2023051612210442100_bty960-B7","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/humu.21628","article-title":"ENIGMA\u2013evidence-based network for the interpretation of germline mutant alleles: an international initiative to evaluate risk and clinical significance associated with sequence variation in BRCA1 and BRCA2 genes","volume":"33","author":"Spurdle","year":"2012","journal-title":"Hum. Mutat"},{"key":"2023051612210442100_bty960-B8","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1101\/gr.118638.110","article-title":"Loss of exon identity is a common mechanism of human inherited disease","volume":"21","author":"Sterne-Weiler","year":"2011","journal-title":"Genome Res"},{"key":"2023051612210442100_bty960-B9","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1038\/ejhg.2011.100","article-title":"Contribution of bioinformatics predictions and functional splicing assays to the interpretation of unclassified variants of the BRCA genes","volume":"19","author":"Th\u00e9ry","year":"2011","journal-title":"Eur. J. Hum. Genet"},{"key":"2023051612210442100_bty960-B10","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1002\/humu.22973","article-title":"Adding in silico assessment of potential splice aberration to the integrated evaluation of BRCA gene unclassified variants","volume":"37","author":"Vall\u00e9e","year":"2016","journal-title":"Hum. 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