Functional interleukin-7 receptor α-chain (IL-7Rα) genetic variants, which affect alternative splicing and expression of the soluble IL-7Rα, are associated with susceptibility to autoimmunity. We previously described aberrant IL-7Rα expression and impaired IL-7-mediated T-cell functions in tuberculosis patients. In the present study, we investigated a possible role of IL7RA gene variants. Six exonic IL7RA polymorphisms were genotyped and two minor alleles were found at lower frequencies in tuberculosis patients as compared to healthy contacts from Ghana (rs11567764, p = 0.002; rs1494558, p = 0.01). The rs11567764 polymorphism tags an IL7RA haplotype exclusively found in African populations and was predicted to affect splicing of exon 5. Reduced mRNA expression of the Δexon_5-6 variant was found in T-cells from carriers of the protective rs11567764 allele. Although we were not able to demonstrate the causative effect of rs11567764, our findings suggested functional implications of genetic variants on IL-7Rα splicing and with potential impact on T-cell protection against tuberculosis.