CFTR rs74551134: Understanding This Splice-Site Variant
The rs74551134 variant, also known as 3849+10kbC>T, is a genetic change in the CFTR gene that disrupts normal RNA splicing. It is recognized as a pathogenic variant associated with cystic fibrosis, often resulting in a milder disease phenotype due to residual protein function.
What each genotype means
Typical CFTR genotype
This genotype represents the common, non-variant sequence at this specific location in the CFTR gene. It is not associated with the splicing defects linked to cystic fibrosis carrier status for this variant.
This is the most common genotype found in all human populations.
Cystic fibrosis carrier status
This genotype indicates you carry one copy of the pathogenic variant c.3718-2477C>T, also known as 3849+10kbC>T. This variant is known to cause aberrant splicing of the CFTR protein, and individuals with this variant are considered carriers for cystic fibrosis. Please discuss these results and any implications for family planning with a genetic counselor or your healthcare provider.
This genotype is rare in the general population but is found at elevated frequencies in Ashkenazi Jewish and European populations.
Potential cystic fibrosis risk
This genotype indicates you carry two copies of the pathogenic variant c.3718-2477C>T. Because this variant is associated with cystic fibrosis, individuals with this genotype may be at risk for the condition or related CFTR-associated disorders. Please consult with a medical professional or a clinical geneticist to discuss the clinical significance of this finding.
This genotype is extremely rare in the general population.
What is the rs74551134 Variant?
The rs74551134 variant is a specific change in the DNA sequence of the CFTR gene, technically identified as c.3718-2477C>T or 3849+10kbC>T. It is classified as a splice-site variant, meaning it occurs in an intronic region—a non-coding part of the gene that is typically removed during the process of creating messenger RNA (mRNA). When this specific nucleotide change occurs, it interferes with the cellular machinery responsible for splicing, often causing the inclusion of an extra, non-functional segment of genetic code into the final mRNA transcript. This leads to the production of an abnormal CFTR protein. Because this variant is located deep within an intron, it is not always detected by standard exome sequencing, which primarily focuses on the protein-coding exons of genes. Instead, it is often identified through targeted genetic testing panels designed to screen for common cystic fibrosis-related mutations.
The Role of the CFTR Gene
The CFTR gene provides instructions for making the cystic fibrosis transmembrane conductance regulator protein. This protein functions as a channel that transports negatively charged chloride ions into and out of cells. This movement of ions is essential for maintaining the proper balance of salt and water on cell surfaces, which in turn keeps mucus thin and free-flowing in organs like the lungs, pancreas, and digestive tract. When the CFTR gene contains pathogenic variants, the resulting protein may be absent, non-functional, or produced in insufficient quantities. This leads to the buildup of thick, sticky mucus, which is the hallmark of cystic fibrosis. Because rs74551134 allows for a small amount of normally spliced, functional mRNA to be produced, individuals with this variant often retain some residual CFTR activity, which can result in a less severe clinical presentation compared to variants that completely abolish protein function.
Clinical Associations and Research
Research has firmly established rs74551134 as a pathogenic variant linked to cystic fibrosis. Clinical studies indicate that the severity of the condition in individuals carrying this variant is influenced by the amount of aberrant versus normal splicing that occurs. Because some transcripts are spliced correctly, the body can still produce a small amount of functional CFTR protein, estimated at approximately eight percent of normal levels. This residual function is significant because it can modify the disease course, often leading to a milder phenotype. In recent years, the development of CFTR modulator therapies has changed the treatment landscape for many patients. Clinical evidence supports the use of these modulators for individuals carrying this variant, as the drugs can help improve the function of the residual protein produced by the cells. Patients should always consult with their healthcare provider or a specialized genetic counselor to discuss how specific genetic findings relate to their personal health and potential treatment options.
Understanding Your Results
If you have received information about your status regarding rs74551134, it is important to understand that this is a carrier-status marker. Cystic fibrosis is an autosomal recessive condition, meaning that an individual typically needs to inherit two pathogenic variants—one from each parent—to manifest the disease. Carrying a single copy of this variant generally does not cause cystic fibrosis symptoms, but it is relevant for family planning and reproductive health. Because this variant is rare in the general population but more frequent in specific ancestral groups, such as those of European or Ashkenazi Jewish descent, testing is often included in carrier screening panels. This information is intended for educational purposes and should not be used to diagnose or treat any medical condition. Always discuss your genetic test results with a qualified clinician or a genetic counselor who can provide context based on your full medical history and family background.
How common is this variant?
The rs74551134 variant is rare, with a global allele frequency of approximately 0.0003 in the gnomAD database, though it shows higher prevalence in European and Ashkenazi Jewish populations.
Frequently asked questions
Is rs74551134 the same as 3849+10kbC>T?
Yes, rs74551134 and 3849+10kbC>T are different names for the same genetic variant. The former is the reference SNP ID used in databases, while the latter is a common clinical nomenclature describing its location within the CFTR gene.
Does having this variant mean I have cystic fibrosis?
Not necessarily. Cystic fibrosis is an autosomal recessive condition, meaning it usually requires two pathogenic variants to cause the disease. If you have only one copy, you are typically a carrier and may not show symptoms.
Can this variant be treated with medication?
Yes, some CFTR modulator therapies have been approved for patients with specific CFTR variants, including 3849+10kbC>T. You should discuss your specific genotype and treatment eligibility with your doctor or a pharmacist.
Why is this variant sometimes missed in genetic tests?
Because it is located deep within an intron, it is not always captured by standard exome sequencing, which focuses on protein-coding regions. It is usually detected by targeted panels specifically designed to look for known cystic fibrosis mutations.
Sources & further reading
Educational information only, last refreshed 10/15/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Severe pathogenic mutation (p.Gly542Ter) associated with cystic fibrosis.
Classic cystic fibrosis in-frame 3-bp deletion variant (p.Phe508del / deltaF508) causing misfolding and impaired chloride channel trafficking.
Pathogenic frameshift mutation (c.3659delC) in CFTR linked to cystic fibrosis.
Pathogenic nonsense variant (p.Gly542Ter / G542X) causing autosomal recessive cystic fibrosis when inherited in trans with another CFTR pathogenic allele.
Also known as p.Arg117His (R117H), this CFTR variant is associated with mild or atypical cystic fibrosis and congenital bilateral absence of the vas deferens, with clinical severity influenced by the poly-T tract background.
A CFTR mutation associated with cystic fibrosis and CFTR-related disorders.