Submissions for variant NM_012452.3(TNFRSF13B):c.61+11G>C

dbSNP: rs201483236

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002218033	SCV002362318	likely benign	Immunodeficiency, common variable, 2	2025-01-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003235671	SCV003933896	benign	not specified	2023-05-19	criteria provided, single submitter	clinical testing	Variant summary: TNFRSF13B c.61+11G>C alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00033 in 251236 control chromosomes. The observed variant frequency is approximately 100 fold of the estimated maximal expected allele frequency for a pathogenic variant in TNFRSF13B causing Common Variable Immunodeficiency phenotype (2.9e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.61+11G>C in individuals affected with Common Variable Immunodeficiency and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.