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It is designed for clinicians and researchers who wish to assess the potential impact of the considerable number of non-coding variants found in Whole Genome Sequencing runs. It annotates individual variants with underlying regulatory features in an intuitive way by assessing over 100 genome-wide annotations. Additionally, it calculates a score, which reflects the regulatory potential of the variant region. Its dichotomous classifications, \u2018functional\u2019 or \u2018non-functional\u2019, and a human-readable presentation of the underlying evidence allow a biologically meaningful interpretation of the score. The output shows key aspects of every variant and allows rapid access to more detailed information about its possible role in gene regulation. RegulationSpotter can either analyse single variants or complete VCF files. Variants located within protein-coding transcripts are automatically assessed by MutationTaster as well as by RegulationSpotter to account for possible intragenic regulatory effects. RegulationSpotter offers the possibility of using phenotypic data to focus on known disease genes or genomic elements interacting with them. RegulationSpotter is freely available at https:\/\/www.regulationspotter.org.<\/jats:p>","DOI":"10.1093\/nar\/gkz327","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T15:21:10Z","timestamp":1557415270000},"page":"W106-W113","source":"Crossref","is-referenced-by-count":22,"title":["RegulationSpotter: annotation and interpretation of extratranscriptic DNA variants"],"prefix":"10.1093","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7048-208X","authenticated-orcid":false,"given":"Jana Marie","family":"Schwarz","sequence":"first","affiliation":[{"name":"Department of Neuropediatrics, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany"},{"name":"Centrum f\u00fcr Therapieforschung, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany"},{"name":"NeuroCure Cluster of Excellence and NeuroCure Clinical Research Center, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3382-122X","authenticated-orcid":false,"given":"Daniela","family":"Hombach","sequence":"additional","affiliation":[{"name":"Centrum f\u00fcr Therapieforschung, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany"},{"name":"NeuroCure Cluster of Excellence and NeuroCure Clinical Research Center, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5316-1399","authenticated-orcid":false,"given":"Sebastian","family":"K\u00f6hler","sequence":"additional","affiliation":[{"name":"Centrum f\u00fcr Therapieforschung, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany"},{"name":"Berlin Institute of Health (BIH), Berlin, Germany"},{"name":"Einstein Center for Digital Future, Berlin, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8943-8484","authenticated-orcid":false,"given":"David N","family":"Cooper","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics, Cardiff University, Cardiff, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2824-3891","authenticated-orcid":false,"given":"Markus","family":"Schuelke","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany"},{"name":"NeuroCure Cluster of Excellence and NeuroCure Clinical Research Center, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9746-4412","authenticated-orcid":false,"given":"Dominik","family":"Seelow","sequence":"additional","affiliation":[{"name":"Centrum f\u00fcr Therapieforschung, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany"},{"name":"Berlin Institute of Health (BIH), Berlin, Germany"}]}],"member":"286","published-online":{"date-parts":[[2019,5,20]]},"reference":[{"key":"2019062808124862900_B1","doi-asserted-by":"crossref","DOI":"10.1017\/S0016672315000166","article-title":"The long tail and rare disease research: the impact of next-generation sequencing for rare Mendelian disorders","volume":"97","author":"Shen","year":"2015","journal-title":"Genet. 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