Assessed by IARC on December 2, 2019 during meeting 46.

The committee considered IGHV4-59*01_S8652 (T109C) of Genotype B16 of submission S00010, which was previously evaluated as IGHV4-59*01_S5140 of submission S00006 at Meeting 12. It was affirmed as a Level 0 sequence at that time.

The sequence was seen in 3.03% of all unmutated rearrangements, with 18133 sequences including 8545 perfect matches to the inferred allele. There was abundant variation in the CDR3 regions of the aligned sequences. One other IGHV4-59 allele was present in the genotype, as well as two IGHV4-4 sequences and one IGHV4-61 sequences. Haplotype data is supportive of the inference, though the haplotype ratios likely reflect the presence of some chimeric sequences within the dataset. The ratios for the two IGHV4-59 sequences were 77:23 for the inference and 19:81 for the *01 allele, suggesting that the sequences are carried on different chromosomes. The sequence, up to and including nucleotide 319, was affirmed as a Level 1 sequence, but was subsequently identified as the recently reported allele IGHV4-59*11. The sequence submitted to Genbank lacked the 320th nucleotide that is noted in the IMGT sequence. In IARC and OGRDB communications, a dot at the 3’ end of the sequence shows that the IARC believes there is a nucleotide missing from the sequence. The affirmed sequence will be submitted to IMGT as IGHV4-59*i02, as a record of the rearrangability (and therefore likely functionality) of the sequence.