Splicing is an integral part of pre-mRNA processing involving the removal of introns and joining of exons. A number of different transcripts can be produced in a process called alternative splicing, which involves the differential usage of splice sites in different developmental times, tissues, or individuals. However, not much is known regarding the genetic determinants of splice site usage in alternative splicing, albeit its importance in altering the mRNA and potentially protein function. Previously, our group focused on individual variation in individual splice site usage and mapped thousands of genomic variants that affect splice site choice. Here, we used two different approaches to test the causality of the previously determined associations. First, we used minigene constructs with altered polymorphisms to test whether they would affect splice site choice in human cell culture. Our findings indeed support that nucleotide polymorphisms beyond the known consensus splice site sequences can affect splice site choice. Second, we used CRISPR base-editing on single nucleotide polymorphisms (SNPs) and tested whether these SNPs are causal polymorphisms for the genetic associations. We used specific sets of criteria to select representative SNPs and designed sgRNAs for each of them. We selected cell lines that harbour the major alleles at the associated loci in such a way that the effects of editing can be potentially tested. We present the results of this ongoing project. Our findings shed light on the genetic determinants of splicing and can provide novel insights into splice site choice.