ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.-18C>G

dbSNP: rs34135787
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000445652 SCV001363917 pathogenic beta Thalassemia 2019-07-29 criteria provided, single submitter clinical testing Variant summary: HBB c.-18C>G is located in the untranslated mRNA region upstream of the initiation codon. The variant was absent in 250902 control chromosomes (gnomAD). The variant, c.-18C>G, has been reported in the literature in multiple individuals affected with Beta Thalassemia Intermedia (Ho_1996, Traeger-Synodinos_1996, Bento_2000). These data indicate that the variant is likely to be associated with disease. At least two publications reported experimental evidence evaluating an impact on protein function, and demonstrated a moderate decrease in mRNA levels compared to the wild type that supports the mechanisms for causing Beta Thalassemia Intermedia (Ho_1996, Sgourou_2004). One ClinVar submission (evaluation after 2014) cited the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV002522736 SCV003439557 pathogenic not provided 2023-06-29 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 393704). For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant alters HBB gene expression (PMID: 8562944, 15009072). This variant is also known as +33 C>G. This variant has been observed in individual(s) with autosomal recessive beta thalassemia intermedia (PMID: 8562944, 10756381). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This variant occurs in a non-coding region of the HBB gene. It does not change the encoded amino acid sequence of the HBB protein.
GeneReviews RCV000445652 SCV000537292 not provided beta Thalassemia no assertion provided literature only

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