CFTR rs113993964: Carrier Status and Splicing Effects
The genetic variant rs113993964 is an intronic alteration in the CFTR gene, located near an essential splice junction. It is classified under carrier status and plays a role in cystic fibrosis and CFTR-related disorders when inherited alongside another disease-causing mutation. Because cystic fibrosis follows an autosomal recessive inheritance pattern, possessing a single copy typically confers carrier status rather than active clinical disease.
What each genotype means
Typical CFTR genotype
This genotype represents the most common state where both copies of the CFTR gene do not carry this specific variant. It is considered the baseline or reference state for this location in the gene.
This is the most common genotype, found in the vast majority of the global population.
Carrier status
You carry one copy of this variant, which is a known splice-site mutation in the CFTR gene. Being a carrier typically does not cause cystic fibrosis symptoms, but it is important to discuss this result with a genetic counselor or physician, especially if you are planning a family, as this condition is inherited in an autosomal recessive pattern.
This genotype is rare, with an allele frequency of approximately 0.00015 in non-Finnish European populations.
Potential cystic fibrosis risk
This genotype indicates that both copies of your CFTR gene carry this variant. Because this variant is associated with defective channel maturation and cystic fibrosis, individuals with this genotype should consult with a medical geneticist or specialist to understand their clinical health status and potential for disease manifestation.
This genotype is extremely rare in the general population.
Genomic Location and the CFTR Gene
The variant rs113993964 sits within an intronic region of the CFTR gene, which resides on human chromosome 7. The CFTR gene provides instructions for making the cystic fibrosis transmembrane conductance regulator protein, an ion channel that transports negatively charged chloride and thiocyanate ions across epithelial cell membranes. Proper chloride transport maintains the balance of fluid and salt on mucosal surfaces throughout the body, including the lungs, pancreas, gastrointestinal tract, and reproductive system. In typical physiology, accurate cellular machinery must splice out non-coding introns to join protein-coding exons together into mature messenger RNA (mRNA). Because rs113993964 alters sequence within a critical splice-acceptor region, it can compromise this precise RNA assembly process. Instead of producing fully functional channel proteins, erroneous transcripts can cause defective maturation, degradation, or an absence of mature CFTR channels at the epithelial surface.
Molecular Mechanism and Splice-Site Disruption
Splice-site variants like rs113993964 disrupt the normal recognition signals required by the cellular spliceosome. When the splice-recognition motifs in CFTR introns are altered, the processing machinery may skip entire adjacent exons or incorporate non-functional pseudo-exons into the mature transcript. Experimental models and functional studies demonstrate that splice disruptions in CFTR often lead to drastically reduced levels of full-length, glycosylated protein reaching the apical membrane. Instead, aberrant transcripts undergo nonsense-mediated mRNA decay or yield misfolded proteins that are targeted for premature proteasomal degradation within the endoplasmic reticulum. This dramatic drop in functional ion channels impairs normal chloride efflux and causes secondary hyperabsorption of sodium and water. Consequently, epithelial surfaces become covered with thick, dehydrated secretions that plug airways, block pancreatic ducts, and impair mucosal clearance.
Clinical Significance and Disease Association
Cystic fibrosis is an autosomal recessive condition, meaning an individual generally develops classic disease only when harboring two pathogenic CFTR variants—one inherited from each parent. Databases such as ClinVar and expert consensus groups document that variants in this region can act as disease-causing alleles in a recessive or compound heterozygous state. When paired in trans with another severe mutation, such as the common F508del variant, individuals can exhibit classical cystic fibrosis characterized by progressive pulmonary obstruction, recurrent respiratory infections, and pancreatic exocrine insufficiency. In other instances, depending on overall residual channel activity, variants affecting this locus have been linked to milder CFTR-related disorders, including isolated congenital bilateral absence of the vas deferens (CBAVD) or idiopathic chronic pancreatitis. Evidence for this specific variant is categorized as limited relative to common classic variants, largely due to its rarity and variable expressivity across different genetic backgrounds.
Population Frequency and Demographics
Population genomics datasets, such as the Genome Aggregation Database (gnomAD), indicate that rs113993964 is a rare allele. Its minor allele frequency is estimated at approximately 0.00015 (around 0.015%) in non-Finnish European populations, and it is observed at even lower frequencies or remains undetected in many non-European global cohorts. Because of this rarity, it was not historically included in standard minimal pan-ethnic carrier screening panels, such as the standard 23-variant carrier panel established by the American College of Medical Genetics and Genomics (ACMG). However, modern comprehensive next-generation sequencing assays and expanded carrier panels are increasingly capable of identifying this and other uncommon splice-site variants.
Interpreting Results and Practical Next Steps
Discovering a variant at rs113993964 through genetic testing does not mean a person will develop cystic fibrosis. Carriers who possess only one copy of an altered CFTR allele are typically healthy and asymptomatic because the remaining normal allele produces sufficient functional protein to maintain mucosal hydration. The primary relevance of single-allele carrier status lies in reproductive planning: if a person and their reproductive partner both carry a pathogenic CFTR variant, there is a 25% chance with each pregnancy of having a child with cystic fibrosis. Anyone with questions regarding carrier screening results, family planning options, or personal symptoms should consult a certified genetic counselor or medical geneticist to review their full clinical context and testing methodology.
How common is this variant?
The rs113993964 variant is very rare in global populations, with an estimated allele frequency of approximately 0.00015 (0.015%) in non-Finnish European cohorts in gnomAD, and it is even less frequent across other ancestries.
Frequently asked questions
Does carrying the rs113993964 variant mean I have cystic fibrosis?
No. Carrying one copy of this variant typically confers carrier status rather than active clinical disease. Cystic fibrosis requires pathogenic variants on both copies of the CFTR gene to manifest.
Can carriers of CFTR variants experience any symptoms?
The vast majority of cystic fibrosis carriers live completely healthy, normal lives without symptoms. However, rare individuals carrying one variant may have a mildly increased susceptibility to certain CFTR-related conditions, such as recurrent pancreatitis or sinusitis.
What is the reproductive risk if I am a carrier for this variant?
If your biological partner is also a carrier of a disease-causing CFTR variant, there is a 25% chance in each pregnancy that the child will inherit both variants and develop cystic fibrosis. A certified genetic counselor can provide detailed carrier risk assessment for both partners.
Why was this variant not detected on my standard carrier screen?
Many older or standard carrier screening panels only test for a small set of the most common mutations, such as the ACMG-recommended 23-variant panel. Because rs113993964 is very rare, it is usually only identified by comprehensive full-gene sequencing.
Sources & further reading
Educational information only, last refreshed 9/8/2026. 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.