Why use it

Critical for post-test counseling in expanded carrier screening (ECS). Avoids the clinical error of treating a negative screen as a complete exclusion. Quantifies the safety margin provided by the test and allows couples to make truly informed reproductive decisions.

About

When an individual tests negative on a carrier screening panel, their risk of being a carrier is dramatically reduced — but never reaches zero. This is because no panel has 100% detection rate (sensitivity). Mutations missed by the assay remain undetected. Using Bayes theorem, this calculator computes the precise "residual carrier risk" after a negative result, and propagates that risk to estimate the probability of having an affected child based on the partner's carrier status.

When to use

Post-test counseling after a negative expanded carrier screening result
When one partner is a known carrier and the other has a negative panel result
Comparing detection rates between targeted genotyping panels vs. sequencing approaches
Explaining why a negative result is reassuring but not a guarantee

Formula

Prior Risk (p) = 1 / carrier_frequency_denominator Sensitivity (s) = detection_rate / 100 Residual Carrier Risk: = [p × (1 − s)] / [p × (1 − s) + (1 − p) × 1] Offspring Risk (partner = known carrier): = Residual Risk × 1.0 × (1/4) Offspring Risk (partner = untested, population freq): = Residual Risk × Population Carrier Freq × (1/4)

Pearls & pitfalls

Residual Risk = [Prior × (1 − DR)] / [Prior × (1 − DR) + (1 − Prior) × 1]
The higher the Detection Rate (sequencing > genotyping), the lower the residual risk.
For CF genotyping panels (90% DR) in Caucasians (prior 1/25): residual risk ≈ 1 in 241.
For CF sequencing (>99% DR) in the same population: residual risk drops to ≈ 1 in 2,500+.
Always use ethnicity-specific detection rates — panels are calibrated to common mutations in specific ancestries.
A negative result in a low-prior-risk population provides greater reassurance than in a high-prior-risk population.

Next steps

Communicate the residual risk clearly. If the residual carrier risk is unacceptably high for the couple (especially when the other partner is a known carrier), discuss: (1) next-generation sequencing of the gene if only genotyping was performed; (2) PGT-M (Preimplantation Genetic Testing for Monogenic Disorders); (3) Prenatal diagnosis (CVS or amniocentesis).

Evidence

Standard Bayesian calculation universally taught in genetic counseling and clinical genetics training programs. Endorsed by ACMG, SMFM, and ACOG for post-carrier-screening counseling. Applied in all major clinical genetics textbooks (Thompson & Thompson, Nussbaum et al.).

References

ACOG Committee Opinion 690: Carrier Screening in the Age of Genomic Medicine. Obstet Gynecol. 2017;129(3):e35-e40. — link
Gregg AR et al. Expanding carrier screening: ACMG practice resource. Genet Med. 2021;23(10):1793-1806. — link
Beaudet AL, Belmont JW. Array-Based DNA Diagnostics: Let the Revolution Begin. Annu Rev Med. 2008;59:113-129. — link

Residual Carrier Risk (Negative Screen)

Calculator