•  The human SLC4A7 gene and the mouse Slc4a7 gene each have alternative promoters that can yield two groups of NBCn1 variants, one in which the extreme N terminus begins with MEAD (representing the first four residues of the N‐terminal domain (Nt)) and the other in which it begins with MERF. •  The mouse Slc4a7 gene contains, and the human SLC4A7 gene is predicted to contain, a novel exon that encodes an alternatively spliced cassette IV of 20 aa in the cytoplasmic Nt domain of NBCn1. This new cassette IV is in a position homologous to that of a previously described cassette in the Nt of NBCn2. •  From combinations of known optional structural elements (OSEs), SLC4A7 is theoretically able to produce 32 major variants, of which 16 have now been identified, 10 for the first time in the present study. •  With heterologous expression in Xenopus oocytes, the OSEs have strong effects on surface abundance and intrinsic HCO3− transport activity. Cassettes II, III and the novel cassette IV have stimulatory effects on the intrinsic HCO3− transport activity of NBCn1. Abstract  The SLC4A7 gene encodes the electroneutral sodium/HCO3 cotransporter NBCn1, which plays important physiological and pathophysiological roles in many cell types. Previous work identified six NBCn1 variants differing in the sequence of the extreme N terminus – MEAD in rat only, MERF in human only – as well as in the optional inclusion of cassettes I, II, and III. Earlier work also left open the question of whether optional structural elements (OSEs) affect surface abundance or intrinsic (per‐molecule) transport activity. Here, we demonstrate for the first time that SLC4A7 from one species can express both MEAD‐ and MERF‐NBCn1. We also identify a novel cassette IV of 20 aa, and extend by 10 the number of full‐length NBCn1 variants. The alternative N termini and four cassettes could theoretically produce 32 major variants. Moreover, we identify a group of cDNAs predicted to encode just the cytosolic N‐terminal domain (Nt) of NBCn1. A combination of electrophysiology and biotinylation shows that the OSEs can affect surface abundance and intrinsic HCO3− transport activity of NBCn1, as expressed in Xenopus oocytes. Specifically, MEAD tends to increase whereas novel cassette IV reduces surface abundance. Cassettes II, III and novel cassette IV all appear to increase the intrinsic activity of NBCn1.