Submissions for variant NM_000416.3(IFNGR1):c.538G>A (p.Gly180Arg)

gnomAD frequency: 0.00142  dbSNP: rs137854904

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002228217	SCV001097049	likely benign	Disseminated atypical mycobacterial infection	2024-01-05	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001081307	SCV001314754	benign	Immunodeficiency 27A	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003398706	SCV004122245	benign	not specified	2023-10-27	criteria provided, single submitter	clinical testing	Variant summary: IFNGR1 c.538G>A (p.Gly180Arg) results in a non-conservative amino acid change located in the Interferon gamma receptor, D2 domain, poxvirus/mammal (IPR021126) 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 0.001 in 251252 control chromosomes in the gnomAD database, including 1 homozygote. To our knowledge, no occurrence of c.538G>A in individuals affected with Interferon Gamma Receptor Deficiency 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. All submitters classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Breakthrough Genomics, Breakthrough Genomics	RCV000097415	SCV005227762	likely benign	not provided		criteria provided, single submitter	not provided
Human Evolutionary Genetics, Institut Pasteur	RCV000097415	SCV000121629	not provided	not provided		no assertion provided	not provided
PreventionGenetics, part of Exact Sciences	RCV003925100	SCV004740920	likely benign	IFNGR1-related disorder	2021-05-07	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).