It can be challenging to determine the DNA strand and allele designations for a single nucleotide polymorphism (SNP) because strand designations and orientation can differ depending on the database or assembly referenced (e.g., NCBI genome build updates). To address this issue, Illumina developed the top/bottom (TOP/BOT) strand and A/B allele nomenclature using sequence-based context to assign DNA strand orientation that allows the same allele calls over time regardless of database or genome build used.
For SNPs that are not [A/T] or [G/C], A is always on the top strand and T is always the bottom strand. A and T nucleotides are the “A alleles”; G and C nucleotides are the “B alleles”.
If the SNP is [A/T] or [G/C]: Use sequence walking to determine TOP/BOT strands, then assign A/B alleles.
For TOP strands: For [A/T] SNPs, Allele A = “A” and Allele B = “T.” For [G/C] SNPs, Allele A = “C” and Allele B = “G.”
For BOT strands: For [A/T] SNPs, Allele A = “T” and Allele B = “A.” For [G/C] SNPs, Allele A = “G” and Allele B = “C.”
For more information, see the Tech note “TOP/BOT” Strand and “A/B” Allele