DHCR7 rs28941772: Understanding This Smith-Lemli-Opitz Variant
The genetic variant rs28941772, also known as c.964-1G>C, is a pathogenic splice-site mutation located within the DHCR7 gene. It is primarily recognized for its association with Smith-Lemli-Opitz syndrome, an autosomal recessive condition characterized by impaired cholesterol biosynthesis.
What each genotype means
Typical risk
You carry two reference copies of this DHCR7 locus and do not carry the c.964-1G>C pathogenic splice variant. This result indicates you are not a carrier for this specific cause of Smith-Lemli-Opitz syndrome. Because carrier screening evaluates specific variants, it does not completely eliminate the possibility of rare, unassayed variants elsewhere in the DHCR7 gene.
Carried by over 98% to 99% of people across most global populations.
SLOS carrier status
You carry one copy of the pathogenic c.964-1G>C (IVS8-1G>C) variant, making you an asymptomatic carrier of autosomal recessive Smith-Lemli-Opitz syndrome. Carriers do not experience classic symptoms of the disorder, as one functional copy of the DHCR7 gene typically maintains sufficient enzyme activity. Reproductive risk is primarily relevant if your partner is also a carrier for a pathogenic DHCR7 variant, which can be evaluated through reproductive genetic counseling.
Carried by approximately 1% to 2% of individuals of European ancestry and around 0.7% of African Americans; it is much less common in East Asian populations.
High risk for SLOS
This genotype indicates two copies of the c.964-1G>C null splice variant in DHCR7, a pattern strongly associated with Smith-Lemli-Opitz syndrome. In medical literature, homozygosity for this severe variant disrupts cholesterol biosynthesis and is associated with severe multi-system congenital features or high early mortality. Clinical confirmation and consultation with a medical geneticist are essential to contextualize these genetic findings.
Extremely rare across all populations, occurring in fewer than 1 in 100,000 individuals globally.
What is the rs28941772 Variant?
The variant rs28941772 is a specific change in the DNA sequence of the DHCR7 gene, often referred to in clinical literature as c.964-1G>C or IVS8-1G>C. This variant is classified as a splice-site mutation, meaning it occurs at a critical junction where the cellular machinery processes genetic instructions. By altering this site, the mutation disrupts the normal splicing process, which can lead to the production of a non-functional or truncated protein. Because this variant interferes with the fundamental assembly of the DHCR7 enzyme, it is considered a null mutation, meaning it effectively prevents the gene from performing its intended biological task. It is widely documented in clinical databases as a significant pathogenic variant, meaning it is strongly linked to the development of specific genetic conditions when inherited in a particular pattern.
The Role of the DHCR7 Gene
The DHCR7 gene provides the instructions for the body to create an enzyme called 7-dehydrocholesterol reductase. This enzyme is responsible for the final step in the complex process of cholesterol biosynthesis, where it converts 7-dehydrocholesterol into cholesterol. Cholesterol is a vital molecule in the human body, serving as a key component of cell membranes, a precursor for various hormones, and a necessary element for the protection of nerve cells. When the DHCR7 gene contains pathogenic mutations, the resulting enzyme is either absent or unable to function correctly. This leads to a buildup of 7-dehydrocholesterol and a corresponding deficiency in cholesterol levels. Because cholesterol is essential for normal development, these metabolic disruptions can result in the diverse physical and developmental features observed in individuals with Smith-Lemli-Opitz syndrome.
Research and Clinical Associations
Research has established that rs28941772 is one of the most common pathogenic variants associated with Smith-Lemli-Opitz syndrome. Because the condition is autosomal recessive, an individual must typically inherit two copies of a pathogenic variant—one from each parent—to manifest the syndrome. Carriers, who possess only one copy of the variant, generally do not exhibit the symptoms of the disorder. Clinical studies have identified this specific mutation in a significant proportion of individuals diagnosed with the syndrome, making it a primary target for molecular diagnostic testing. While the association between this variant and the syndrome is well-supported by clinical evidence, the severity of the condition can vary significantly between individuals, even among those with similar genetic profiles. This variability suggests that other genetic and environmental factors may also influence how the condition presents.
Population Frequency
The rs28941772 variant is considered rare in the general population, with a frequency typically reported as less than 0.01% in large-scale databases like gnomAD. However, carrier frequencies can vary significantly across different ethnic and ancestral groups. Studies focusing on expanded carrier screening have indicated that while the variant is rare overall, it accounts for a substantial percentage of identified carriers in certain populations, particularly among those of European ancestry. Because it is a recessive condition, the rarity of the variant means that the likelihood of two carriers having a child with the syndrome is low, but it remains a focus of clinical screening programs designed to provide prospective parents with information regarding their reproductive risks.
Interpreting Your Genetic Information
If you have received information regarding your status for the rs28941772 variant, it is important to understand that this is a carrier status result. Being a carrier does not mean you have or will develop Smith-Lemli-Opitz syndrome. This information is primarily used for reproductive planning and family health history assessment. Genetic testing results should never be used to self-diagnose or make medical decisions without professional guidance. If you are concerned about your carrier status or potential risks to future children, the most appropriate step is to consult with a certified genetic counselor or a medical geneticist. These professionals can help you interpret your results in the context of your personal and family history, explain the implications of autosomal recessive inheritance, and discuss available testing options for your partner or family members.
How common is this variant?
The rs28941772 variant is rare, with a frequency of less than 0.01% in the general population, though it is a frequent cause of Smith-Lemli-Opitz syndrome among carriers in specific ancestral groups.
Frequently asked questions
What is Smith-Lemli-Opitz syndrome?
Smith-Lemli-Opitz syndrome is a rare, autosomal recessive genetic disorder caused by a deficiency in the enzyme 7-dehydrocholesterol reductase. This deficiency disrupts cholesterol production, leading to various developmental and physical anomalies.
Does having one copy of the rs28941772 variant mean I have the syndrome?
No, having one copy of the variant makes you a carrier. Because the condition is autosomal recessive, you would typically need to inherit a pathogenic variant from both parents to be affected by the syndrome.
How is Smith-Lemli-Opitz syndrome diagnosed?
Diagnosis is typically confirmed through biochemical testing, which measures levels of cholesterol and 7-dehydrocholesterol in the blood. Genetic testing for variants in the DHCR7 gene may also be used to confirm the diagnosis.
Should I be tested for this variant?
Genetic testing is often recommended for individuals with a family history of the syndrome or for those undergoing expanded carrier screening. You should discuss the necessity and implications of this testing with a healthcare provider or genetic counselor.
Sources & further reading
Educational information only, last refreshed 10/8/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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