ClinVar Miner

Submissions for variant NM_000397.3(CYBB):c.170C>A (p.Ala57Glu) (rs151344481)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000059253 SCV000567361 pathogenic not provided 2015-08-07 criteria provided, single submitter clinical testing The A57E missense variant in the CYBB gene has been reported previously in association with X-linkedchronic granulomatous disease (Ariga et al., 1993). It was not observed in approximately 6,500 individuals ofEuropean and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not acommon benign variant in these populations. A57E is a non-conservative amino acid substitution, which islikely to impact secondary protein structure as these residues differ in polarity, charge, size and/or otherproperties. This substitution occurs at a position that is conserved across species and in-silico analysispredicts this variant is probably damaging to the protein structure/function. In addition, missense variants innearby residues (A53D, R54G/M/S, A55D, P56L, C59R/F/Y/W, N63K, C64R, M65R, L66P) have beenreported in the Human Gene Mutation Database in association with chronic granulomatous disease (Stenson etal., 2014), supporting the functional importance of this region of the protein. Therefore, we interpret A57E as a pathogenic variant.
Invitae RCV000815331 SCV000955780 uncertain significance Chronic granulomatous disease, X-linked 2018-11-29 criteria provided, single submitter clinical testing This sequence change replaces alanine with glutamic acid at codon 57 of the CYBB protein (p.Ala57Glu). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with X-linked chronic granulomatous disease (PMID: 8101486, 10914676). ClinVar contains an entry for this variant (Variation ID: 68391). This variant has been reported to affect CYBB protein function (PMID: 21659519). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
UniProtKB/Swiss-Prot RCV000059253 SCV000090782 not provided not provided no assertion provided not provided

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