Submissions for variant NM_002185.5(IL7R):c.412G>A (p.Val138Ile)

gnomAD frequency: 0.72524  dbSNP: rs1494555

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen	RCV000015965	SCV004242294	benign	Immunodeficiency 104	2024-01-23	reviewed by expert panel	curation	NM_002185.5(IL7R):c.412G>A is a missense variant predicted to cause substitution of Valine by Isoleucine at amino acid 138 (p.Val138Ile). The filtering allele frequency (the lower threshold of the 95% CI of 65661/74940 alleles) of the c.412G>A variant in IL7R is 0.8743 for African/African American chromosomes by gnomAD v.4, which is higher than the ClinGen SCID VCEP threshold (>0.00566) for BA1 and therefore meets this criterion (BA1). Additionally, 367924 homozygous have been described. In summary, this variant meets the criteria to be classified as Benign for autosomal recessive SCID, based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP. Criteria applied: BA1 (VCEP specifications version 1).
PreventionGenetics, part of Exact Sciences	RCV000121214	SCV000308737	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000015965	SCV000457143	benign	Immunodeficiency 104	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000121214	SCV000539381	benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 1 paper published in 1998 claimed variant was pathogenic for SCID based on identification in 1 proband.
Mendelics	RCV000015965	SCV001136819	benign	Immunodeficiency 104	2019-05-28	criteria provided, single submitter	clinical testing
Pathology and Clinical Laboratory Medicine, King Fahad Medical City	RCV000121214	SCV001438932	benign	not specified		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000015965	SCV001720365	benign	Immunodeficiency 104	2025-02-03	criteria provided, single submitter	clinical testing
GeneDx	RCV001711072	SCV001943006	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 20952689, 21326139, 18687755)
Genome-Nilou Lab	RCV000015965	SCV001980935	benign	Immunodeficiency 104	2021-08-19	criteria provided, single submitter	clinical testing
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	RCV000121214	SCV004233015	benign	not specified	2024-01-24	criteria provided, single submitter	clinical testing	This variant is classified as Benign based on local population frequency. This variant was detected in 83% of patients studied by a panel of primary immunodeficiencies. Number of patients: 79. Only high quality variants are reported.
Breakthrough Genomics, Breakthrough Genomics	RCV001711072	SCV005299857	benign	not provided		criteria provided, single submitter	not provided
OMIM	RCV000015965	SCV000036232	uncertain significance	Immunodeficiency 104	1998-12-01	no assertion criteria provided	literature only
ITMI	RCV000121214	SCV000085385	not provided	not specified	2013-09-19	no assertion provided	reference population
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000121214	SCV001742615	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000121214	SCV001932121	benign	not specified		no assertion criteria provided	clinical testing
GenomeConnect, ClinGen	RCV001711072	SCV002074671	not provided	not provided		no assertion provided	phenotyping only	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing.