ClinVar Miner

Submissions for variant NM_000383.4(AIRE):c.1567-5C>T (rs192215705)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000241567 SCV000345077 benign not specified 2016-08-29 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000241567 SCV000051956 benign not specified 2018-06-26 criteria provided, single submitter clinical testing Variant summary: AIRE c.1567-5C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 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 0.0027 in 274874 control chromosomes, predominantly at a frequency of 0.0095 within the South Asian subpopulation in the gnomAD database, including 5 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 3-folds higher than 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 South Asian origin. To our knowledge, no occurrence of c.1567-5C>T in individuals affected with Autoimmune Polyglandular Syndrome Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as "benign." Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000029310 SCV000754675 benign Polyglandular autoimmune syndrome, type 1 2017-12-07 criteria provided, single submitter clinical testing
PreventionGenetics RCV000241567 SCV000303916 likely benign not specified criteria provided, single submitter clinical testing

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