Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001175347 | SCV000052601 | uncertain significance | not specified | 2024-01-25 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.-106G>C (also referred to as -56G>C) alters a non-conserved nucleotide located in the untranscribed promoter region upstream of the HBB gene, and therefore might affect gene expression. The variant allele was found at a frequency of 0.00035 in 31394 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in HBB causing Beta Thalassemia Intermedia (0.00035 vs 0.011), allowing no conclusion about variant significance. The variant, c.-106G>C, has been reported in the literature in a compound heterozygous patient together with a beta thalassemia major disease variant (c.92+1G>A), who had a beta thalassemia intermedia phenotype (Agouti_2008). The variant was also found in a homozygous individual, who displayed some features resembling to beta thalassemia minor, i.e. mild microcytic anemia, with low mean corpuscular hemoglobin concentration (Douzi_2015). These reports suggest that the variant might cause a milder phenotype, possibly affecting the beta gene expression. However, the variant was also reported in eight heterozygous individuals showing normal hematological values (i.e. being impossible to distinguish it from healthy, non-carrier subjects), and in at least three compound heterozygote patients carrying other globin disease variants, who showed phenotypes equivalent to patients carrying only the other alleles (Vinciguerra_2018, Belmokhtar_2022); therefore, these data suggest a benign role for the variant. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 18081706, 25754248, 21423179, 27718361, 26076395, 29157184, 35615994). ClinVar contains an entry for this variant (Variation ID: 36281). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759788 | SCV000889357 | uncertain significance | not provided | 2020-08-19 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV001004364 | SCV001163302 | uncertain significance | Hb SS disease | criteria provided, single submitter | clinical testing | ||
Mayo Clinic Laboratories, |
RCV000759788 | SCV001714973 | uncertain significance | not provided | 2020-01-18 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV002290956 | SCV002583271 | uncertain significance | Beta-thalassemia HBB/LCRB | criteria provided, single submitter | clinical testing | ||
The ITHANET community portal, |
RCV000029946 | SCV001244533 | pathogenic | beta Thalassemia | 2019-11-25 | no assertion criteria provided | curation | |
Natera, |
RCV000029946 | SCV002091634 | uncertain significance | beta Thalassemia | 2021-04-23 | no assertion criteria provided | clinical testing |