We provide a set of scripts for simulating, estimating, and visualizing the relationship between common, small effect variant Polygenic Burden (PB) and Large-Effect Variant (LEV). We present a mathematical and summary statistics based framework that utilizes the relationship between PB and LEV among cases for some methodologically-and clinically-relevant applications. Details can be found in our manuscript ‘Contextualizing genetic risk score for disease screening and rare variant discovery’. For questions on the software, please contact Eric R. Gamazon, PhD (at ericgamazon@gmail.com). Please cite: Dan Zhou, Dongmei Yu, Jeremiah M. Scharf, Carol A. Mathews, Lauren McGrath, Edwin Cook, S Hong Lee, Lea K. Davis§, Eric R. Gamazon§. Contextualizing genetic risk score for disease screening and rare variant discovery. Dan Zhou & Eric R. Gamazon. (2021). A mathematical and summary statistics based framework for the analysis of polygenic risk score and large-effect variants. Zenodo. https://zenodo.org/record/4767933