Originally assessed by IARC on May 11, 2018.

“The sequence is present at a moderate frequency (0.5%), in the IgDiscover analysis. No information was provided by the submitter regarding analysis with partis or TIgGER. Haplotype analysis could not be performed. Analysis for chimerism did not provide evidence against the existence of the sequence.
Extensive analysis was submitted, including four additional IgDiscover analyses using modified germline gene reference datasets. Although IARC were strongly persuaded by the submitted data, it was agreed that the sequence should be moved to Level 0. Issues relating to the end nucleotides deserve wider discussion by the Working Group before IMGT is notified of such a potentially controversial decision. This will be raised by AC at the forthcoming WG meeting.”

It has been noted that neither partis not TIgGER had been able to infer IGHV3-7*02 or any variant thereof while these tools inferred IGHV3-7*01 (see supplementary information privided with the submission ).

(April 12, 2019) In line with IARC policy, the submitted sequence was recognized up to and including nucleotide 319. A trailing “.” indicates IARC’s opinion that the sequences likely to contain an additional/additional 3’ nucleotide(s) for which there is insufficient evidence to make an affirmation.

(August 7th 2019) At the 40th meeting of the IARC, the committee considered the inference of this sequence in S00028. The committee noted a rearrangement frequency of 0.7%, with 10188 alignments, though only 2443 perfect matches to the inferred allele. Alignments were also seen to three other IGHV3-7 sequences, though only one of these sequences was abundant (IGHV3-7*03: 20569 alignments, 4062 unmutated alignments). Haplotyping based on IGHJ6 alleles confirmed the segregation of reads associated with the two abundant alleles to the different haplotypes. Alignments to the *01 allele were at a trivial level (<0.01% of ‘unmutated’ alignments), though alignments to the *02 allele were seen in 0.09% of all unmutated sequences. They likely originated from an introduction of A318 as part of the V-DJ rearrangement process. This represented 3% of all alignments to the IGHV3-7 gene. There were 933 different CDR3s associated with the inference, including 233 different CDR3s associated with unmutated alignments. The committee agreed that the sequence should be accepted as a valid inference, which raises this sequence from Level 0 to Level 2. In line with previous policy, the submitted sequence is recognized up to and including nucleotide 319. A trailing “.” in the affirmed sequence indicates the 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 IGHV3-7*02_A318G with 12640 sequences and 2796 perfect matches and 269 Unique CDR3s with unmutated Seqs. In this analysis only one other allele of IGHV3-7 was seen (as very rare inferences had been removed by IgDiscover filtering), IGHV3-7*03 with 21677 sequences and 4120 perfect matches giving a 37:63 allelic ratio. These alleles were very well separated by IGHJ6-based haplotype analysis (100:0 and 1:99, respectively). The re-analysis thus confirmed the inference of IGHV3-7*i01 as a Level 2 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.