The 40th meeting of the IARC on August 7th 2019 considered the sequence IGHV3-53*02_S0744. The sequence represents IGHV3-53*02 C288T in the IMGT numbering system. The committee noted a rearrangement frequency of 0.7%, with 5149 alignments including 2426 perfect matches to the inferred allele. Alignments were also seen to three other IGHV3-53 sequences, though only one of these sequences was abundant (IGHV3-53*04: 3448 alignments, 2149 unmutated alignments). Haplotyping based on IGHJ6 alleles confirmed the segregation of reads associated with these two alleles to the different haplotypes Alignments to the two other alleles shown in the genotype were at trivial levels (<0.01% of ‘unmutated’ alignments, in each case). There were 742 different CDR3s associated with the inference, including 292 different CDR3s associated with unmutated alignments. The committee agreed that the sequence should be accepted as a Level 1 sequence as IGHV3-53*i01. In line with previous policy, the submitted sequence was recognized up to and including nucleotide 319. A trailing “.” in the affirmed sequence indicates IARC’s opinion that the sequence is likely to contain an additional 3’ nucleotide for which there is insufficient evidence to make an affirmation.

Reanalysis of the original submission at Meeting 43 of the IARC on October 7, 2019 again identified the same novel allele IGHV3-53*02_S0744 (IGHV3-53*02 C288T) with 5425 sequences aand 2447 perfect matches and 300 Unique CDR3s with unmutated Seqs. In this analysis only one other allele of IGHV3-53 was seen (as very rare inferences had been removed by IgDiscover filtering), IGHV3-53*04 with 3551 sequences and 2163 perfect matches giving a 60:40 allelic ratio. These alleles were very well separated by IGHJ6-based haplotype analysis (1:99 and 99:1, respectively). The re-analysis thus confirmed the inference of IGHV3-53*i01 as a Level 1 sequence. In line with previous policy, the submitted sequence is recognized up to and including nucleotide 319. A trailing “.” in the affirmed sequence indicates IARC’s opinion that the sequence is likely to contain an additional 3’ nucleotide for which there is insufficient evidence to make an affirmation.