--- title: Implementation of ACMG Guidelines Whitepaper description: Learn in more about the reasoning behind the implementation of VarSome's ACMG classifier, one of the key-stone features provided by the VarSome Suite --- [![VarSome](https://landing.varsome.com/hubfs/VarSome_February2020%20Theme/Images/logo.png)](https://varsome.com/) - Editions - [More about VarSome.com](https://varsome.com/varsome-editions/varsome/) - [More about VarSome Premium](https://varsome.com/varsome-editions/varsome-premium/) - [More about VarSome Clinical](https://varsome.com/varsome-editions/varsome-clinical/) - [Learn more about APIs](https://varsome.com/information/varsome-api-info/) - About - Resources - [Library](https://varsome.com/library/) - [Documentation](https://docs.varsome.com/) - [Query types](https://varsome.com/about/examples/) - [IVDR](https://landing.varsome.com/ivdr-whitepaper) - [Germline Classification](https://varsome.com/about/resources/acmg-implementation/) - [Somatic Classification](https://varsome.com/about/resources/amp-implementation/) - Partners - [Distributors](https://varsome.com/distributors/) - [Partners](https://varsome.com/partners/) - [Become a partner](https://landing.varsome.com/become-varsome-partner) - General - [The Company](https://saphetor.com/about/) - [Cite VarSome](https://varsome.com/about/varsome-citations/) - [Link to VarSome](https://varsome.com/how-do-i-create-link-varsome/) - [Contact](https://landing.varsome.com/contact) - [Community](https://varsome.com/community-contributions/) - [Blog](https://blog.varsome.com/) [Sign in](https://varsome.com/sign-in/) [Join](https://varsome.com/sign-up/) WHITEPAPER # VarSome’s Implementation of ACMG Guidelines Learn in more about the reasoning behind the implementation of VarSome's ACMG classifier, one of the key-stone features provided by the VarSome Suite: - About ACMG - Interpretation Process - Implemented Rules - Unimplemented Rules ![Screenshot 2023-02-24 at 13.24.46](https://landing.varsome.com/hubfs/Screenshot%202023-02-24%20at%2013.24.46.png) [![Download now!](https://no-cache.hubspot.com/cta/default/4384097/072b0901-7815-4cbf-bd88-2ce4858998f4.png)](https://cta-redirect.hubspot.com/cta/redirect/4384097/072b0901-7815-4cbf-bd88-2ce4858998f4) ### VarSome’s Implementation of ACMG Guidelines [![Download now!](https://no-cache.hubspot.com/cta/default/4384097/072b0901-7815-4cbf-bd88-2ce4858998f4.png)](https://cta-redirect.hubspot.com/cta/redirect/4384097/072b0901-7815-4cbf-bd88-2ce4858998f4) ![About ACMG](https://landing.varsome.com/hubfs/screenshot_43.png) ## About ACMG Our implementation is derived from the ”Standards and guidelines for the interpretation of sequence variants” was published in 2015 by Sue Richards et al. in their seminal paper ([ACMG Guidelines](https://www.acmg.net/docs/Standards_Guidelines_for_the_Interpretation_of_Sequence_Variants.pdf)). Following the advice from our clinical advisors, feedback from the VarSome user community, and using statistically justified thresholds we always strive to provide the most accurate and up-to-date implementation!   ![Interpretation Process](https://landing.varsome.com/hubfs/screenshot_47.png) ## Interpretation Process Clinical Evidence is the foundation stone of our ACMG evaluation and is derived from [a multitude of sources](https://varsome.com/datasources/). The data are then integrated into the implementation of all the rules requiring clinical evidence and the calculation of gene statistics. Splice site prediction and conservation tests are performed as well, to be utilized in the respective rules. Allele frequencies are taken into an account for the implementation of certain rules. Finally, selecting a specific transcript can modify the ACMG verdict and the user can select a transcript through the VarSome UI. This complex process requires the involvement of numerous databases for the formation of the ACMG classifier. ![Implemented Rules](https://landing.varsome.com/hubfs/screenshot_48-1.png) ## Implemented rules Our ACMG classifier has currently 21 implemented rules. Each rule comes with a default strength recommended by ACMG. However, it is allowed to reduce or enhance the strength of a rule depending on the available annotatioon data. VarSome's ACMG implementation makes use of this flexibility and allows users who disagree with a given implementation make their own modifications using VarSome UI. ![Patient-specific Rules](https://landing.varsome.com/hubfs/screenshot_49.png) ## Patient-specific Rules Certain rules are not implemented or not currently available to VarSome users - in most cases, this is because the necessary data required to evaluate the rules is not in the public-domain, or the rules require patient-specific information, sometimes on a per-variant basis. Should they have more evidence, users can manually toggle rules on or off, or adjust the strength used, and the resulting classification will be re-evaluated immediately. ###### Interested in our Solutions? ## Get in touch for a demo and consultation Loading... ## Latest News [See all blog posts](https://blog.varsome.com) ![](https://landing.varsome.com/hubfs/VarSome_February2020%20Theme/Images/logo.png) - VarSome Suite - [VarSome.com](https://saphetor.com/varsome-editions/varsome/) - [VarSome Premium](https://saphetor.com/varsome-editions/varsome-premium/) - [VarSome Clinical](https://saphetor.com/varsome-editions/varsome-clinical/) - [VarSome API](https://varsome.com/information/varsome-api-info/) - System Status - [System Status](http://status.saphetor.com/) - Resources - [Query Examples](https://varsome.com/about/examples/) - [Documentation](https://docs.varsome.com/) - [Help Center](https://docs.varsome.com/en) - [Cite VarSome](https://news.varsome.com/en/cite-varsome-the-human-genomic-variant-search-engine) - The Company - [About Saphetor SA](https://saphetor.com/about/) - [News](https://blog.varsome.com) - [Distributors](https://landing.varsome.com/distributors) - [Contact](https://saphetor.com/contact/) - Legal - [Terms of Use](https://varsome.com/terms/) - [Privacy Policy](https://varsome.com/privacy/) VarSome Suite is brought to you by [Saphetor SA](https://saphetor.com). © 2024 Saphetor SA – All Rights Reserved.