BRCA1 rs386833395: Understanding Your Cancer Risk
The rs386833395 variant is a well-studied deletion in the BRCA1 gene, historically known as 185delAG (or c.68_69delAG). When present, this pathogenic loss-of-function mutation causes premature protein truncation, disrupting normal cellular DNA repair mechanisms. Inheriting this variant is strongly associated with Hereditary Breast and Ovarian Cancer (HBOC) syndrome, significantly elevating the lifetime risk of developing breast, ovarian, and related cancers.
What each genotype means
Typical risk profile
You carry two reference copies of the BRCA1 sequence at this position. This result does not confer the elevated hereditary cancer risks associated with the pathogenic truncation variant at this locus. However, it does not rule out other genetic risk factors across BRCA1, BRCA2, or the wider genome.
Carried by more than 99.99% of individuals across all major global ancestries.
High hereditary cancer predisposition
You carry one copy of the pathogenic nonsense allele (c.315T>A, p.Tyr105Ter), which introduces a premature stop codon that disrupts BRCA1 protein function. Statistical research associates this loss-of-function change with significantly elevated lifetime risks of breast, ovarian, and related cancers in hereditary breast and ovarian cancer syndrome. Individuals with this genotype should review their personal and family history with a clinical geneticist or genetic counselor for comprehensive evaluation.
Extremely rare; observed at a minor allele frequency under 0.00001 in global reference panels such as gnomAD.
Genetic Identity and Molecular Nature of rs386833395
Located on chromosome 17 within the BRCA1 gene, rs386833395 represents a two-base deletion often described in historical literature as 185delAG or 187delAG, and formally annotated in HGVS nomenclature as NM_007294.4:c.68_69del (p.Glu23ValfsTer17). Because of local repetitive sequence architecture, it has also been indexed in databases under variant identifiers such as rs796856605. At the molecular level, the loss of these two nucleotides alters the coding reading frame beginning at codon 23. This frameshift quickly introduces a premature stop signal 17 codons downstream, triggering nonsense-mediated decay of the messenger RNA or producing an incomplete, nonfunctional fragment of the BRCA1 protein.
The Biological Role of BRCA1 in Genomic Stability
The BRCA1 gene provides essential instructions for making a tumor suppressor protein that plays a central role in maintaining cellular genome integrity. Working alongside other repair proteins, BRCA1 is critical for homologous recombination, a high-fidelity pathway responsible for repairing dangerous double-strand breaks in DNA. When one copy of BRCA1 carries a loss-of-function change such as rs386833395, the cell's ability to mend everyday DNA damage is compromised if the remaining normal copy is disrupted. This deficiency leads to chromosomal instability and an accumulation of secondary genetic mutations over time, which greatly accelerates the potential transformation of normal cells into malignant tumors.
Clinical Significance and Disease Associations
Multiple international clinical testing panels and expert consensus groups classify rs386833395 as pathogenic for Hereditary Breast and Ovarian Cancer syndrome. Female carriers face substantial cumulative lifetime risks, historically estimated between 56% to 83% for breast cancer and 14% to 58% for ovarian cancer by age 70. Beyond breast and ovarian malignancies, research has associated loss-of-function BRCA1 alleles with elevated risks of pancreatic cancer and aggressive forms of prostate cancer in male carriers. Unlike common complex traits that involve subtle polygenic effects, this single variant carries high penetrance, though cancer development remains probabilistic rather than inevitable.
Population Frequency and Founder Heritage
In the broad global population, rs386833395 is exceptionally rare, with an overall allele frequency far below 0.1% across multi-ancestry panels like the Genome Aggregation Database (gnomAD). However, it represents one of three classic founder mutations in individuals of Ashkenazi Jewish ancestry. In this community, the carrier frequency is markedly higher, reaching approximately 0.8% to 1.0% (an allele frequency around 0.4%). While heavily documented in Ashkenazi lineages, the deletion has also been independently observed in clinical cohorts across European, Latin American, and other global backgrounds.
Navigating Results: Clinical Context and Limitations
Direct-to-consumer genotyping platforms sometimes screen for this specific mutation, but raw data or consumer-grade reports should never be treated as formal diagnostic confirmation. Analytical artifacts and false positives can occur in microarrays, necessitating confirmation through targeted, clinical-grade Sanger or next-generation sequencing in an accredited medical genetics laboratory. Furthermore, a negative test for rs386833395 does not rule out hereditary cancer predisposition, as thousands of other distinct pathogenic mutations exist across the BRCA1 and BRCA2 genes. Anyone reviewing family histories of cancer or personal genetic results should consult a certified genetic counselor or physician for personalized risk assessment and surveillance guidance.
How common is this variant?
The rs386833395 deletion is extremely rare globally (gnomAD MAF < 0.0001 in non-founder groups), but exists as a well-characterized founder mutation occurring in roughly 1 in 100 individuals (allele frequency ~0.4%) of Ashkenazi Jewish ancestry.
Frequently asked questions
What does a positive result for rs386833395 mean?
A positive finding means you have inherited the 185delAG pathogenic deletion in the BRCA1 gene, which confers a higher lifetime risk of breast, ovarian, pancreatic, and prostate cancers. It is not a cancer diagnosis, as some individuals with the variant never develop cancer. Any unconfirmed result should be evaluated by a healthcare professional and verified via clinical diagnostic testing.
Why is this variant also called 185delAG or c.68_69del?
The mutation was originally described as 185delAG based on historical numbering of the BRCA1 complementary DNA sequence. Modern standardized HGVS nomenclature designates the deletion as NM_007294.4:c.68_69del because the deleted pair of bases resides at positions 68 and 69 of the modern coding sequence.
Does having normal alleles at rs386833395 mean I am safe from BRCA mutations?
No. Testing negative for rs386833395 only indicates you do not carry this specific two-base deletion. There are thousands of other known pathogenic mutations in BRCA1 and BRCA2 that are not captured by a single variant test, which is why comprehensive multi-gene panels are used in clinical evaluations.
How common is rs386833395 in the general public?
Across most worldwide populations, this variant is exceedingly rare and unobserved in most reference samples. However, due to historical founder effects, it is present in approximately 0.8% to 1.0% of individuals of Ashkenazi Jewish descent.
What should I do if my raw genetic data shows rs386833395?
Raw consumer data has a recognized rate of false-positive findings for rare indels and should never be used to make medical choices. You should consult a licensed genetic counselor or physician, who can order a certified clinical diagnostic test to confirm your genetic status and discuss appropriate screening guidelines.
Sources & further reading
Educational information only, last refreshed 9/13/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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