More than 10,000 variants are linked to autoimmune diseases and over 90% of disease-associated genetic variants identified through genome-wide association studies reside in the non-coding genome, including distal regulatory elements (DREs). However, the molecular mechanisms underlying these DREs and any functional consequences of genetic variants within them remain largely untested and unclear. Here we observed an autoimmune risk locus, CD83ΒΈ containing 3 fine-mapped SNPs linked with rheumatoid arthritis, found in open chromatin in B cells. Among the 3 risk variants, rs74405933 (G>A), is located on a CD83-regulating, CRISPR activation (CRISPRa)-responsive DRE and is predicted to disrupt a NF-KB transcription factor binding motif. To measure the impact of rs74405933 on CD83 expression, prime editing was used to introduce the risk allele A (rs74405933) into human B cells. A depletion in the frequency of the risk allele in the CD83 high-expression quantile suggests an association between SNP rs74405933 and reduced CD83 expression. Beyond rs74405933, other SNPs found in open chromatin regions within the locus must also be tested to uncover their contribution to CD83 regulation. To comprehensively map and quantify DREs in an unbiased manner, we have designed a tiled CRISPRa library spanning a 300 kb region, targeting a 200 bp window in primary human B cells. The enrichment of gRNAs in the top 20% of CD83-expressing cells will reveal CRISPRa-responsive regions corresponding to functional DREs. This facilitates further investigation into how these SNPs within the identified DRE regions influence phenotypes such as target gene expression. Next, we aim to establish a scalable toolkit for prioritizing non-coding genetic variants and reveal DRE mechanisms at high resolution, with potential applications to other loci and diseases.