CFTR rs113993966: What Your Genotype Means
The genetic variant rs113993966 represents a missense change (c.350G>A, p.Arg117His or R117H) in the CFTR gene. In medical genetics, it is recognized as a variable-expressivity, low-penetrance pathogenic variant associated with CFTR-related disorders, atypical cystic fibrosis, and congenital bilateral absence of the vas deferens (CBAVD). Because clinical outcomes depend heavily on additional genetic variations on the same chromosome, its presentation ranges widely from completely asymptomatic to progressive pulmonary disease.
What each genotype means
Typical CFTR Function
You carry two reference copies of the CFTR gene at position c.350, showing no presence of the R117H missense alteration. This genotype does not confer an elevated inherited risk for CFTR-related disorders or variable-expressivity cystic fibrosis at this locus. Typical population carrier risks for other CFTR variants elsewhere in the gene may still apply.
Found in more than 99.4% of individuals globally, including approximately 99.4% to 99.7% of individuals of European descent.
CFTR Variant Carrier
You carry one copy of the c.350G>A (p.Arg117His or R117H) variant, designating you as a carrier of an allele associated with variable-expressivity CFTR conditions. Carrier status alone typically does not cause classical cystic fibrosis, but clinical expressivity can vary depending on what CFTR variants exist on the other chromosome and nearby poly-T/TG splice tract variants (such as 5T or 7T) on the same chromosome. Genetic counseling and carrier screening are commonly considered for family planning.
Carried by approximately 1 in 300 to 1 in 350 individuals of European ancestry (~0.3%), but is substantially rarer in East Asian and African populations.
Variable CFTR Risk
You carry two copies of the R117H (p.Arg117His) alteration in the CFTR gene. Published studies indicate this genotype is linked to a variable clinical spectrum ranging from asymptomatic status to CFTR-related disorders such as congenital bilateral absence of the vas deferens (CBAVD) or mild cystic fibrosis, strongly modulated by the co-inherited poly-T splice tract variants (5T, 7T, or 9T). Comprehensive clinical evaluation and genetic counseling are recommended to interpret individual clinical context.
Extremely rare across all populations, occurring in fewer than 1 in 100,000 individuals globally.
Genetic Architecture of rs113993966
The variant rs113993966 sits in the CFTR gene, located on human chromosome 7. At the molecular level, this single nucleotide polymorphism involves a change from guanine to adenine at cDNA position 350 (c.350G>A), which substitutes the amino acid arginine with histidine at codon 117 (p.Arg117His, commonly written as R117H). CFTR encodes an epithelial chloride and bicarbonate channel essential for maintaining ion and fluid balance across mucosal membranes in the respiratory tract, pancreas, gastrointestinal system, and reproductive organs. Biochemically, R117H is classified as a gating mutation that leads to reduced channel conductance and altered open-state probability, producing a protein channel that reaches the cell surface but functions with diminished efficiency.
Phenotypic Spectrum and the Poly-T Modifier
The clinical impact of rs113993966 exhibits profound variable expressivity and depends on whether it occurs alongside other variants. Cystic fibrosis is an autosomal recessive disorder, typically requiring two pathogenic alleles to cause disease. For individuals carrying R117H along with another CFTR pathogenic variant on the second chromosome, the clinical presentation is heavily influenced by a noncoding polythymidine tract (poly-T tract) in intron 8 on the same chromosome (in cis). When R117H is linked in cis with the 5T allele (c.1210-34TG[12]T[5]), exon skipping increases dramatically, resulting in significantly lower functional protein levels and a higher likelihood of classic or moderate cystic fibrosis symptoms. Conversely, when linked with 7T or 9T alleles, individuals frequently remain asymptomatic or present mildly with isolated adult-onset issues, such as congenital bilateral absence of the vas deferens (CBAVD), chronic pancreatitis, or bronchiectasis.
Strength of Scientific Evidence and Clinical Classification
Evidence linking rs113993966 to CFTR-related conditions is extensive and rigorously documented across decades of molecular and clinical study, indexed in ClinVar, PubMed, and CFTR2 registries. The variant is formally classified by expert consensus as pathogenic with low penetrance or variable expressivity. Single-channel electrophysiology studies confirm altered anion conductance, while multicenter screening registries describe diverse presentations depending on phase and trans-acting variants. Despite this extensive evidence base, predicting individual health outcomes based purely on carrier identification remains complex; the presence of the variant alone does not guarantee classic cystic fibrosis, highlighting the distinction between genetic susceptibility and definitive disease manifestations.
Interpreting Results and Clinical Next Steps
Receiving genetic results indicating an rs113993966 variant can cause understandable uncertainty. It is essential to recognize that consumer genotyping results are non-diagnostic and frequently omit phase determination (cis versus trans arrangement) and comprehensive poly-T or TG-repeat analysis. Carriers of a single variant generally do not show systemic cystic fibrosis symptoms, although reproductive counseling is recommended to assess family planning risks. Any individual seeking clarity regarding CFTR findings should consult a certified genetic counselor or medical geneticist. Diagnostic confirmation typically involves comprehensive diagnostic sequencing, haplotype resolution, and physiological assessments such as sweat chloride testing.
How common is this variant?
According to the Genome Aggregation Database (gnomAD), the overall global allele frequency for rs113993966 is approximately 0.001 to 0.0025, reaching its highest documented frequency in European ancestries at roughly 0.26% to 0.3%. Homozygotes are exceptionally uncommon in general population datasets.
Frequently asked questions
Does having the rs113993966 variant mean I have cystic fibrosis?
No, carrying one copy of rs113993966 (R117H) does not mean you have cystic fibrosis. Cystic fibrosis is an autosomal recessive condition that typically requires disease-causing variants on both copies of the CFTR gene. In addition, R117H is a mild, variable-expressivity variant whose effects depend heavily on other genetic elements.
What is the poly-T tract and why does it matter for R117H?
The poly-T tract is a noncoding region in intron 8 of the CFTR gene that influences how efficiently the gene's instructions are processed. When R117H occurs on the same chromosome as a short 5T tract, CFTR protein production is reduced, increasing the risk of respiratory or classic symptoms. When paired with longer 7T or 9T tracts, significantly more working protein is made, often leading to minimal or no symptoms.
Can rs113993966 cause male infertility?
Yes, men who inherit R117H alongside another pathogenic CFTR variant may develop congenital bilateral absence of the vas deferens (CBAVD), which prevents sperm from entering the ejaculate. This is considered an isolated CFTR-related disorder and typically does not affect overall health, lifespan, or non-reproductive organ systems.
What should I do if a direct-to-consumer DNA test detects this variant?
Direct-to-consumer testing is not a clinical diagnosis and often lacks context regarding phase or modifier variants like the poly-T tract. You should discuss your findings with a physician or genetic counselor, who can arrange comprehensive diagnostic sequencing, clinical evaluation, and sweat chloride testing if indicated.
Sources & further reading
Educational information only, last refreshed 9/9/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Classic cystic fibrosis in-frame 3-bp deletion variant (p.Phe508del / deltaF508) causing misfolding and impaired chloride channel trafficking.
Class III CFTR gating missense variant (p.Gly551Asp, G551D) responsive to the CFTR potentiator ivacaftor (Kalydeco).
Indicates carrier status for cystic fibrosis caused by the severe p.Gly542Ter (G542X) nonsense mutation.
Identifies heterozygous carriers of the frameshift mutation c.3659delC (p.Thr1220Lysfs) linked to autosomal recessive 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.