Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001844510 | SCV002103526 | uncertain significance | not specified | 2022-02-24 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.*132C>A is located in the untranslated mRNA region downstream of the termination codon. The variant lies about 20 nucleotides downstream to the known polyA-tail signal, and thus it would likely not interfere with cleavage of the transcript and addition of polyA tail, however it can still affect potential protein binding sites or miRNA target sites that may influence transcript expression levels. The variant allele was found at a frequency of 7.3e-05 in 150942 control chromosomes, predominantly within the Latino subpopulation at a frequency of 0.00065 in the gnomAD database (v3.1 genomes dataset). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.*132C>A, has been reported in the literature in two compound heterozygous Hispanic individuals, who were affected with Beta Thalassemia Intermedia, and carried a beta-0 variant in trans (Heath_2001, Rizo-de-la-Torre_2020), however, one of these individuals also carried the variant c.*129T>C in cis with the c.*132C>A variant (Heath_2001). These data do not allow clear conclusions about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. However, another variant affecting the same nucleotide, c.*132C>T, has also been reported in individuals affected with Beta Thalassemia Intermedia (PMIDs: 22862814, 31930713), suggesting that variants affecting this 3' UTR region might have functional effect. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Fulgent Genetics, |
RCV002489898 | SCV002783225 | uncertain significance | Dominant beta-thalassemia; Heinz body anemia; Hb SS disease; alpha Thalassemia; Malaria, susceptibility to; METHEMOGLOBINEMIA, BETA TYPE; Erythrocytosis, familial, 6; Hereditary persistence of fetal hemoglobin; Beta-thalassemia HBB/LCRB | 2021-08-18 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478881 | SCV004219840 | uncertain significance | not provided | 2023-03-23 | criteria provided, single submitter | clinical testing | The c.*132C>A variant is located in the 3 prime untranslated region (UTR) of the HBB gene. It has been identified in individuals with beta thalassemia intermedia in trans with the known HBB c.118C>T pathogenic variant (PMIDs: 11279660 (2001) and 32142096 (2020)) and in cis with the HBB c.*129T>C variant (PMID: 11279660 (2001)).Taking into account the available information, we are unable to determine the clinical significance of this variant. Previous names for this variant include Nt494+132C>A. |