Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588894 | SCV000697070 | likely benign | not provided | 2016-03-21 | criteria provided, single submitter | clinical testing | Variant summary: c.-10_-7delAACA affects non-conserved nucleotides, resulting in deletion of 4 nucleotides in the 5UTR region. Mutation taster predicts benign outcome. 4/5 in silico toosl via Alamut predict no significant change on the RNA splicing sites, ESEfinder predicts gain of binding motif for RNA splicing enhancer. However, these predictions should be taken with caution as Alamut tools are meant to analyze UTR regions, however, based on the topology of the region around this mutation does not include any regulatory elements (Sgourou, 2004). This variant was found in 6/121126 control chromosomes at a frequency of 0.0000495, predominantly observed in East Asian subpopulation with MAF of 0.000465 (4/8604 chr), which does not exceed the maximal expected frequency of a pathogenic allele (0.0111803). This variant has been reported both in cis and trans with known b-thal-0 variants in individuals presented with b-thal trait, suggesting that the variant in interest does not contribute to the thalassemic phenotype in these pts. Moreover, 2 individual, heterozygous for the variant of interest, had normal hematological parameters, suggesting that the variant is rare benign polymorphism. Functional studies so far yielded conflicting results ranging from no effect to a minor decrease steady state levels of mRNA to 70.6% compared with the wild type gene when different experimental systems were used (Frances, 1993; Sgourou, 2004). Taking togeter, the variant is likely to be a benign polymorphism, however, more clinical data as well as results of translational studies needed to evaluate the variant with confidence. Therefore, the variant was scored as likely benign until additional information becomes available. |
| The ITHANET community portal, |
RCV001078296 | SCV001244456 | pathogenic | beta Thalassemia | 2019-11-25 | no assertion criteria provided | curation | |
| Natera, |
RCV001078296 | SCV002091626 | likely benign | beta Thalassemia | 2018-10-05 | no assertion criteria provided | clinical testing |