rs1494555
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1
This summary comes from the ClinGen Evidence Repository: 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). LINK:https://erepo.genome.network/evrepo/ui/classification/CA124393/MONDO:0012163/119
Frequency
Consequence
NM_002185.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL7R | NM_002185.5 | c.412G>A | p.Val138Ile | missense_variant | 4/8 | ENST00000303115.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL7R | ENST00000303115.8 | c.412G>A | p.Val138Ile | missense_variant | 4/8 | 1 | NM_002185.5 | P1 | |
IL7R | ENST00000506850.5 | c.412G>A | p.Val138Ile | missense_variant | 4/6 | 2 | |||
IL7R | ENST00000514217.5 | c.412G>A | p.Val138Ile | missense_variant, NMD_transcript_variant | 4/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.714 AC: 108457AN: 151966Hom.: 39716 Cov.: 32
GnomAD3 exomes AF: 0.639 AC: 160614AN: 251166Hom.: 53025 AF XY: 0.639 AC XY: 86677AN XY: 135734
GnomAD4 exome AF: 0.667 AC: 973208AN: 1458140Hom.: 328188 Cov.: 36 AF XY: 0.664 AC XY: 481763AN XY: 725596
GnomAD4 genome ? AF: 0.714 AC: 108523AN: 152084Hom.: 39736 Cov.: 32 AF XY: 0.709 AC XY: 52719AN XY: 74324
ClinVar
Submissions by phenotype
not specified Benign:6Other:1
Benign, criteria provided, single submitter | clinical testing | Pathology and Clinical Laboratory Medicine, King Fahad Medical City | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jan 24, 2024 | 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. - |
Immunodeficiency 104 Uncertain:1Benign:5
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
Uncertain significance, no assertion criteria provided | literature only | OMIM | Dec 01, 1998 | - - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Benign, reviewed by expert panel | curation | ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen | Jan 23, 2024 | 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). - |
not provided Benign:1Other:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 20952689, 21326139, 18687755) - |
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at