Table 1.

Examples of alternative splicing variation in human populations and their functional or pathological consequences.

Gene symbol	Effect of SNP on splicing	Functional or pathological consequence
HMSD	An intronic SNP (rs9945924) causes pronounced skipping of exon 2 by weakening the 5′ splice site.	Generates a novel minor histocompatibility antigen, which affects the immune response and could serve as a potential target for immunotherapy56.
ERAP2	A SNP (rs2248374) residing within the canonical 5′ splice site of exon 10 triggers activation of a downstream cryptic splice site, leading to mRNA nonsense-mediated decay and a significant reduction in the steady-state mRNA level of ERAP218, 57.	Primary lymphocytes homozygous for the G allele express less MHC Class I at the B cell surface, suggesting that this alternative splicing event affects MHC antigen presentation18, 51.
OAS1	A SNP (rs10774671) at the 3′ splice site of exon 7 abolishes splice site activity, resulting in the usage of an internal 3′ splice site.	Produces a protein isoform with reduced enzymatic activity58. Affects the response to interferon (IFN) therapy in hepatitis C patients59, and influences susceptibility to multiple sclerosis65.
SCN1A	An intronic SNP (rs3812718) modulates the alternative splicing of exon 5.	Influences the dose response to antiepileptic drugs60.
IRF5	An intronic SNP (rs2004640) generates a consensus GT 5′ splice site of the alternative first exon 1B, producing an alternative transcript isoform initiated at exon 1B.	Associated with increased risk of systemic lupus erythematosus63, 64.
CD45 (PTPRC)	An exonic SNP (rs17612648) within exon 4 disrupts an exonic splicing silencer, leading to increased inclusion of exon 4.	Associated with multiple sclerosis61.
LDLR	An exonic SNP (rs688) promotes skipping of its exon 12.	Associated with total and LDL-cholesterol levels in females especially in pre-menopausal women67.