Other CHRNA5 rare variants identified in our African-American heavy smoker population (Table 1), included a novel synonymous C>T SNP in exon 1 (G31G), known rare variants in exons 3, 4 and 5 (rs148722844:G>A, V97I, rs2229961:G>A, V134I and rs138719535:T>A, F266I, respectively), and more common known variants in exon 2 (rs79831749:C>T, Y58Y) and exon 5 (rs80087508:A>G, K167R; rs61740655:C>T, T331T; rs79109919:T>A, L363Q and rs16969968:G>A, D398N). Like Haller et al. (2012), no novel polymorphisms were identified in the coding region of CHRNA5 exon 6. Whereas most SNPs detected in our study population were also detected by Haller et al. (2012), they did not report detection of the rare synonymous G31G or non-synonymous V97I SNPs in their African-American study population. The V97I variant was detected in one African-American individual in the NHLBI_ESP re-sequencing study. The individual in our study with the V97I variant also has the L363Q variant, but not the V134I, K167R, F266I or D398N variants. Valine 97 in α5 protein is invariant among species and isoleucine substitution is predicted to be “probably damaging” by PolyPhen2 (http://genetics.bwh.harvard.edu/pph2/). Similar PolyPhen2 predictions are made for V134I,
