ClinVar Miner

Submissions for variant NM_000397.3(CYBB):c.1551T>A (p.Asp517Glu) (rs151344452)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000059246 SCV000511098 likely benign not provided 2016-11-02 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Invitae RCV001083190 SCV000762327 benign Chronic granulomatous disease, X-linked 2020-12-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781320 SCV000919255 benign not specified 2018-12-04 criteria provided, single submitter clinical testing Variant summary: CYBB c.1551T>A (p.Asp517Glu) results in a conservative amino acid change located in the Ferric reductase, NAD binding domain of 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 0.0012 in 193905 control chromosomes, including 75 hemizygous males, predominantly at a frequency of 0.0021 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately equal to the estimated maximal expected allele frequency for a pathogenic variant in CYBB causing X-linked Chronic Granulomatous Disease phenotype (0.0019), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. The variant, c.1551T>A, has been reported in the literature in one individual affected with X-linked Chronic Granulomatous Disease as a benign variant, together with c.90C>A (p.Y30X)(Hill_2010). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
UniProtKB/Swiss-Prot RCV000059246 SCV000090775 not provided not provided no assertion provided not provided
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000059246 SCV001797759 likely benign not provided no assertion criteria provided clinical testing

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