TP53 rs78378471: Understanding the 3' UTR Variant
The genetic variant rs78378471 is a single nucleotide polymorphism located in the 3' untranslated region of the TP53 tumor suppressor gene. By disrupting a critical polyadenylation signal sequence, it alters RNA processing and downregulates the normal production of the p53 protein. Epidemiological studies associate this variant with modified risks for several specific tumor types, including basal cell carcinoma and glioma.
What each genotype means
Typical TP53 polyadenylation signal
This genotype represents the common, expected sequence for the TP53 3' UTR polyadenylation signal. It is associated with normal transcript cleavage and polyadenylation processes in the cell. No specific cancer susceptibility related to this variant is indicated for this genotype.
This is the most common genotype found in the vast majority of the global population.
Altered TP53 polyadenylation signal
This genotype indicates you carry one copy of the variant associated with reduced TP53 transcript cleavage and polyadenylation. Research suggests this variant may confer an altered susceptibility to certain cancer types, such as glioma and basal cell carcinoma. Because the evidence is limited and the variant is rare, you should discuss any personal or family health history concerns with a genetic counselor or physician.
This genotype is rare, with the minor allele frequency observed at less than 0.015 globally.
Variant TP53 polyadenylation signal
This genotype indicates you carry two copies of the variant that affects the TP53 polyadenylation signal. This alteration is linked to reduced efficiency in TP53 transcript processing and has been associated with an increased risk for specific cancers, including glioma and basal cell carcinoma. As this is a rare variant with limited clinical evidence, it is important to consult with a healthcare professional regarding your specific health profile.
This genotype is extremely rare in the general population across all ancestries.
Genetic Location and Molecular Mechanism
The variant rs78378471 (closely evaluated alongside related polyadenylation signal markers in the TP53 locus, such as rs78378222) sits in the noncoding 3' untranslated region (3' UTR) on chromosome 17. Rather than changing an amino acid within the protein sequence, this variant directly alters the canonical polyadenylation signal sequence (AATAAA changed to AATACA). This motif is critical for the cellular machinery that cleaves the pre-messenger RNA and adds a protective poly(A) tail. Consequently, the variant impairs proper 3'-end processing, leading to decreased stability and reduced cellular abundance of TP53 mRNA transcripts.
The Biological Role of the TP53 Gene
TP53 is often described as the 'guardian of the genome.' It encodes the tumor protein p53, a master transcription factor that coordinates cellular responses to genomic stress and DNA damage. When a cell experiences genotoxic insults, p53 activates pathways that pause the cell cycle to allow for DNA repair, or triggers programmed cell death (apoptosis) if the damage is beyond rescue. When steady-state levels of p53 are diminished due to regulatory or post-transcriptional defects, the cell's capacity to maintain genomic stability and eliminate potentially malignant cells becomes compromised.
Cancer Susceptibility and Research Evidence
Genome-wide association studies (GWAS) first identified this polyadenylation signal variant as a moderate-penetrance risk factor for cutaneous basal cell carcinoma. Follow-up investigations in diverse cohorts revealed statistical associations with other malignancies, including glioma, prostate cancer, and colorectal adenoma. However, unlike high-penetrance classical Li-Fraumeni syndrome mutations located in the coding regions of TP53, this noncoding variant does not follow an autosomal dominant, multi-cancer high-penetrance pattern. The overall strength of evidence remains limited and phenotype-specific, with studies noting no elevated risk for certain other common tumors, such as breast cancer.
Population Distribution and Ancestry Trends
The alternative allele at this TP53 polyadenylation locus is uncommon across the globe. Population databases including gnomAD and early genomic surveys report global minor allele frequencies typically well below 0.015 (1.5%). The highest recorded frequencies appear in Northern European populations, particularly within Icelandic cohorts where the variant frequency reaches approximately 1.5% to 2.0%. In contrast, it is observed at substantially lower frequencies or is absent among East Asian and African ancestry populations, illustrating pronounced geographic and ancestral variation.
Clinical Perspective and Limitations
Identifying this variant does not constitute a diagnosis of cancer, nor does it guarantee that an individual will develop any malignancy in their lifetime. Because the variant acts as a modest modifier of statistical risk rather than a deterministic causal mutation, absolute risk remains heavily influenced by family history, lifestyle, and environmental exposures such as UV radiation. Anyone reviewing personal genomic results should discuss their broader health background with a certified genetic counselor or physician before considering alterations to screening or surveillance schedules.
How common is this variant?
The variant is rare globally, exhibiting an overall minor allele frequency under 0.015. It is most frequently documented in populations of Northern European descent (1-2%) and occurs at significantly lower frequencies in other global ancestries.
Frequently asked questions
Does carrying this TP53 variant mean I have Li-Fraumeni syndrome?
No. Li-Fraumeni syndrome is typically caused by high-penetrance coding mutations that disrupt the core functional domains of the p53 protein. This 3' UTR variant alters RNA polyadenylation and confers modest statistical susceptibility to specific tumors, rather than the severe familial syndrome pattern.
Can this genetic variant be used to diagnose cancer?
No, this variant cannot diagnose cancer. It merely represents a statistically measurable risk factor identified in epidemiological cohorts. Most individuals carrying the alternate allele never develop the cancers linked to it.
What cancers have been linked to this variant?
Large genome-wide studies have linked the variant primarily to cutaneous basal cell carcinoma and glioma, with weaker links observed for prostate cancer and colorectal adenoma. Interestingly, research has found no consistent association with breast cancer.
How should I interpret this result from direct-to-consumer testing?
Consumer genetic screening tests have variable validation thresholds and do not provide comprehensive clinical evaluations. If you identify this or any other TP53 variant, review the finding with a genetic counselor or medical provider in the context of your personal and family medical history.
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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Pathogenic missense variant (p.Arg248Gln) associated with Li-Fraumeni syndrome.
Functional codon 72 polymorphism (Arg72Pro) affecting apoptotic capability and associated with differential susceptibility to multiple cancer types.
Functional 3' UTR polyadenylation signal polymorphism altering TP53 transcription termination, showing population-specific baseline carrier frequencies across global groups.
Pathogenic hotspot variant (p.Arg273His) in TP53 predisposing carriers to early-onset sarcomas, breast cancers, and leukemias.
Li-Fraumeni syndrome missense variant (p.Arg248Trp) causing loss of tumor suppressor function and multi-cancer predisposition.
Synonymous and regulatory variant in linkage with TP53 codon 72 that modulates blastocyst implantation competence and the risk of recurrent implantation failure.