ClinVar

Description

Variant summary: TNFRSF13B c.260T>A (p.Ile87Asn) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00046 in 254886 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in TNFRSF13B causing Common Variable Immunodeficiency (0.00046 vs 0.0024), allowing no conclusion about variant significance. c.260T>A has been reported in heterozygous and presumed compound heterozygous state in individuals affected with Common Variable Immunodeficiency (e.g. Bacchelli_2007, Pan-Hammarstrom_2008, PanSalzer_2009, Lougaris_2012, Rojas-Restrepo_2021, Fioredda_2022, Peng_2023, Salih_2023). In some families the variant has been inherited from an unaffected parent and authors described this allele as a risk allele (Peng_2023). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function and showed that this variant resulted in decreased activity (Salzer_2009, Fried_2011, Lougaris_2012). The following publications have been ascertained in the context of this evaluation (PMID: 18978466, 19629655, 17697196, 21419480, 21850030, 22627058, 18200502, 34975878, 18981294, 37678716, 37652172, 35686370). ClinVar contains an entry for this variant (Variation ID: 618436). Based on the evidence outlined above, the variant was classified as likely pathogenic.