rs1494555
Variant summary
Our verdict is Benign. The variant received -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
Publications
- immunodeficiency 104Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
- Omenn syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiencyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -8 ACMG points.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_002185.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| IL7R | TSL:1 MANE Select | c.412G>A | p.Val138Ile | missense | Exon 4 of 8 | ENSP00000306157.3 | P16871-1 | ||
| IL7R | c.412G>A | p.Val138Ile | missense | Exon 4 of 7 | ENSP00000547173.1 | ||||
| IL7R | TSL:2 | c.412G>A | p.Val138Ile | missense | Exon 4 of 6 | ENSP00000421207.1 | P16871-3 |
Frequencies
GnomAD3 genomes AF: 0.714 AC: 108457AN: 151966Hom.: 39716 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.639 AC: 160614AN: 251166 AF XY: 0.639 show subpopulations
GnomAD4 exome AF: 0.667 AC: 973208AN: 1458140Hom.: 328188 Cov.: 36 AF XY: 0.664 AC XY: 481763AN XY: 725596 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.714 AC: 108523AN: 152084Hom.: 39736 Cov.: 32 AF XY: 0.709 AC XY: 52719AN XY: 74324 show subpopulations
Age Distribution
ClinVar
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at