rs72553883

badMag 6.5

This is a variant in the TNFRSF13B gene that changes a alanine to an valine.

Key Literature Trait Associations

Common Variable Immunodeficiency

The T allele causes a p.Ala181Glu (A181E) substitution in the transmembrane domain of TACI, one of the two most common TNFRSF13B mutations found in CVID patients. Screening of 564 unrelated patients with hypogammaglobulinemia identified TACI mutations in approximately 10% of CVID cases, with A181E acting as a dominant-negative that impairs TACI signaling and NF-kB activation. Heterozygous carriers show incomplete penetrance and variable clinical severity.

Salzer U et al. “Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans.” Nature Genetics 37(8):820-828 (2005)

Allele T

OR —

p —

Candidate gene study

Pulvirenti F et al. “Clinical Associations of Biallelic and Monoallelic TNFRSF13B Variants in Italian Primary Antibody Deficiency Syndromes.” Journal of Immunology Research (2016)

Allele T

OR —

p —

N 586

Preliminary work

European

Salzer U et al. “Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes.” Blood (2009)

Allele T

OR —

p 1.0e-3

N 564

Preliminary work

European

Garibyan L et al. “Dominant-negative effect of the heterozygous C104R TACI mutation in common variable immunodeficiency (CVID).” The Journal of Clinical Investigation (2007)

Allele T

OR —

p —

Candidate gene study

European

Immunoglobulin A deficiency

The rs72553883-A allele (p.Ala181Glu) in TNFRSF13B is classified Pathogenic by ClinVar for Immunoglobulin A deficiency type 2 (IgAD2). IgAD and CVID are considered part of a clinical spectrum of primary antibody deficiencies linked to TACI dysfunction. Approximately 13% of IgAD patients carry at least one mutated TNFRSF13B allele, though studies report that monoallelic carriers may not always show clinical differences from wild-type IgAD patients, highlighting the reduced penetrance and polygenic nature of IgAD susceptibility.

Pulvirenti F et al. “Clinical Associations of Biallelic and Monoallelic TNFRSF13B Variants in Italian Primary Antibody Deficiency Syndromes.” Journal of Immunology Research (2016)

Allele A

OR —

p —

N 586

Preliminary work

European

Salzer U et al. “Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans.” Nature Genetics 37(8):820-828 (2005)

Allele A

OR —

p —

N 13