ClinVar Miner

Submissions for variant NM_000074.3(CD40LG):c.684A>G (p.Val228=)

gnomAD frequency: 0.01089  dbSNP: rs11575983
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000547346 SCV000634150 benign Hyper-IgM syndrome type 1 2024-01-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781203 SCV000919089 benign not specified 2018-11-21 criteria provided, single submitter clinical testing Variant summary: CD40LG c.684A>G alters a non-conserved nucleotide resulting in a synonymous change. 4/5 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 0.0035 in 198835 control chromosomes, predominantly at a frequency of 0.035 within the African subpopulation in the gnomAD database, including 8 homozygotes and 172 hemizygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 22-fold of the estimated maximal expected allele frequency for a pathogenic variant in CD40LG causing Hyper IgM Syndrome Type 1 phenotype (0.0016), while the overall frequency of the variant is approximately 2-fold of the estimated maximal expected allele frequency for a pathogenic variant; these data strongly suggest that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.684A>G in individuals affected with Hyper IgM Syndrome Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
PreventionGenetics, part of Exact Sciences RCV003960288 SCV004780649 benign CD40LG-related disorder 2019-03-13 criteria provided, single submitter clinical testing This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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