Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000908282 | SCV001053034 | benign | Polyglandular autoimmune syndrome, type 1 | 2024-01-31 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003330993 | SCV004037917 | likely benign | not specified | 2023-08-16 | criteria provided, single submitter | clinical testing | Variant summary: AIRE c.521G>A (p.Arg174His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00079 in 162342 control chromosomes, predominantly at a frequency of 0.0085 within the East Asian subpopulation in the gnomAD database, including 3 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 3-fold of the estimated maximal expected allele frequency for a pathogenic variant in AIRE causing Autoimmune Polyglandular Syndrome Type 1 phenotype (0.0028), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.521G>A in individuals affected with Autoimmune Polyglandular Syndrome Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Both submitters classified the variant as benign. Based on the evidence outlined above, the variant was classified as likely benign. |
| Natera, |
RCV000908282 | SCV001460102 | benign | Polyglandular autoimmune syndrome, type 1 | 2020-04-20 | no assertion criteria provided | clinical testing |