HBB rs33971440: Understanding Beta-Thalassemia Carrier Status
The rs33971440 variant is a rare genetic change located in the HBB gene that disrupts the production of beta-globin. It is recognized as a pathogenic mutation associated with beta-0 thalassemia, a condition affecting hemoglobin synthesis.
What each genotype means
Typical hemoglobin profile
This genotype represents the common, non-pathogenic sequence for this specific location in the HBB gene. Individuals with this profile do not carry this specific beta-thalassemia mutation.
This is the most common genotype observed in the general population.
Beta-thalassemia carrier status
This genotype indicates you carry one copy of the HBB c.92+1G>A mutation, also known as IVS-I-1 G>A. Carriers are typically asymptomatic, though some may experience mild anemia; you should discuss these results with a healthcare provider to understand your specific health context and reproductive risks.
This genotype is rare in the general population but has been identified at higher frequencies in specific regions, such as parts of Iraq.
Beta-zero thalassemia
This genotype indicates the presence of two copies of the HBB c.92+1G>A mutation, which disrupts the canonical splice donor site and prevents the production of functional beta-globin protein. This is associated with beta-zero thalassemia, a condition that can lead to severe, transfusion-dependent anemia; please consult with a medical specialist for clinical management.
This genotype is extremely rare in the general population.
What is rs33971440?
The variant rs33971440, often referred to in clinical literature as IVS-I-1 G>A, is a single nucleotide change located within the HBB gene. Specifically, it occurs at a critical junction known as a canonical splice donor site. In the process of gene expression, DNA is transcribed into pre-messenger RNA (pre-mRNA), which must then be 'spliced' to remove non-coding segments called introns. This variant alters the genetic code at the start of an intron, effectively preventing the cellular machinery from correctly identifying where the splicing should occur. Because this site is essential for the proper assembly of the HBB transcript, the mutation typically results in a complete loss of functional beta-globin protein production from the affected gene copy, a state often described as beta-0 thalassemia.
The Role of the HBB Gene
The HBB gene provides instructions for making a protein called beta-globin, which is a vital component of hemoglobin. Hemoglobin is the iron-containing protein in red blood cells that carries oxygen from the lungs to the rest of the body. A functional hemoglobin molecule is typically composed of two alpha-globin subunits and two beta-globin subunits. When the HBB gene is mutated, the body may produce insufficient or non-functional beta-globin. This imbalance can lead to the destruction of red blood cells or the production of fewer red blood cells than normal, resulting in anemia. Because humans carry two copies of the HBB gene—one inherited from each parent—the clinical impact of a variant like rs33971440 depends on whether the other copy of the gene is functional.
Research and Clinical Evidence
Scientific research has consistently classified rs33971440 as a pathogenic variant. It has been documented in multiple clinical studies and databases, such as ClinVar and HbVar, as a cause of beta-0 thalassemia. The evidence is grounded in the variant's predictable effect on RNA splicing, which leads to a loss of protein function. While the association with beta-thalassemia is well-established, the clinical presentation in individuals can vary significantly depending on their overall genetic background and the presence of other HBB variants. It is important to note that this variant is considered a carrier-status marker. In an autosomal recessive inheritance pattern, individuals who carry one copy of this variant are typically asymptomatic carriers, while those who inherit two pathogenic variants (or one pathogenic variant combined with another) may experience symptoms of thalassemia.
Population Frequency
The rs33971440 variant is considered rare in the general population. Because it is a specific mutation associated with a hereditary blood disorder, its prevalence is not uniform across all global populations. It is more frequently identified in regions where beta-thalassemia is endemic, though it remains an uncommon finding in large-scale genomic databases. Genetic testing for this variant is typically performed in the context of carrier screening or diagnostic workups for unexplained anemia, rather than as part of routine population-wide health assessments.
Managing Genetic Information
Information regarding your HBB genotype is a tool for understanding your carrier status, not a medical diagnosis. If you have received results indicating you carry this variant, it is essential to discuss the findings with a healthcare provider or a genetic counselor. They can help interpret what this means for your health and provide context regarding family planning or potential risks for offspring. You cannot 'treat' a genetic variant, but understanding your carrier status allows for informed medical decision-making. Always consult with a qualified clinician before making any health-related decisions based on genetic data, and avoid using this information to self-diagnose or alter any prescribed medical treatments.
How common is this variant?
The rs33971440 variant is rare in the general population, with its frequency varying significantly based on ancestral background and regional prevalence of beta-thalassemia.
Frequently asked questions
What does it mean to be a carrier of HBB rs33971440?
Being a carrier means you have one copy of the HBB gene with the rs33971440 mutation and one normal copy. Carriers are usually asymptomatic but can pass the variant to their children.
Is rs33971440 the same as beta-thalassemia?
The variant is a genetic cause of beta-thalassemia. While the variant itself is a mutation, the clinical condition of beta-thalassemia depends on whether you have one or two copies of such mutations.
Should I get tested for this variant?
Genetic testing is typically recommended if you have a family history of thalassemia or if you are planning a family and want to understand your carrier status. Consult a genetic counselor to determine if testing is appropriate for you.
Can I change my HBB genotype?
No, your genetic sequence is inherited and cannot be changed. Genetic information is used to help you and your doctor understand your health risks and make informed decisions.
Sources & further reading
Educational information only, last refreshed 10/1/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This variant in the HBB gene is associated with beta-thalassemia carrier status and potential clinical symptoms of beta-thalassemia intermedia.
This variant causes the substitution of valine for glutamic acid in the beta-globin chain, leading to sickle cell trait or disease depending on zygosity.
A rare structural ancestry-informative single nucleotide variant in the beta-globin locus relevant to population stratification and hemoglobinopathy screening.
Splice junction mutation in HBB (IVS-I-110 G>A) causing beta-plus thalassemia, widely targeted in expanded preconception screening panels.
Classic severe beta-thalassemia nonsense variant (p.Gln40Ter / Codon 39 C>T) routinely included in hemoglobinopathy carrier screening.
A classic nonsense mutation (c.118C>T, p.Gln40Ter, codon 39) causing beta(0)-thalassemia in the homozygous state and defining Mediterranean beta-thalassemia carrier status.