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We developed a Micro Capture-C variant-to-function platform (MCCv) based on analysis of single-allele chromatin structure. This can identify changes in nanoscale chromatin architecture and link variants in\n                    <jats:italic>cis<\/jats:italic>\n                    -regulatory elements to target genes. Furthermore, MCCv can phase other heterozygous variants within a locus to link regulatory variants to allelically imbalanced gene expression and directly read out variant effects on chromatin interactions after genome editing. With this approach, we investigated 405\n                    <jats:italic>cis<\/jats:italic>\n                    -regulatory elements linked to immune-mediated inflammatory disease in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. We uncovered a previously undescribed gain-of-function mechanism, which increases risk of autoimmunity through creation of a neo-CTCF motif that blocks super-enhancer contacts with the\n                    <jats:italic>SESN3<\/jats:italic>\n                    promoter. 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