ClinVar Miner

Submissions for variant NM_000416.3(IFNGR1):c.665A>G (p.His222Arg)

gnomAD frequency: 0.00003  dbSNP: rs768805562
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000767993 SCV000898748 uncertain significance Immunodeficiency 27A; Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency 2018-09-12 criteria provided, single submitter clinical testing IFNGR1 NM_000416.2 exon 5 p.His222Arg (c.665A>G): This variant has not been reported in the literature but is present in 0.1% (29/18870) of East Asian alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/6-137524704-T-C). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV002233764 SCV000956137 uncertain significance Disseminated atypical mycobacterial infection 2024-12-21 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 222 of the IFNGR1 protein (p.His222Arg). This variant is present in population databases (rs768805562, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with IFNGR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 625961). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt IFNGR1 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect IFNGR1 function (PMID: 24199198). 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224411 SCV003920050 uncertain significance Immunodeficiency 27A; Hepatitis B virus, susceptibility to; Helicobacter pylori infection, susceptibility to; Mycobacterium tuberculosis, susceptibility to; Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency 2021-03-30 criteria provided, single submitter clinical testing IFNGR1 NM_000416.2 exon 5 p.His222Arg (c.665A>G): This variant has not been reported in the literature but is present in 0.1% (29/18870) of East Asian alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/6-137524704-T-C). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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