chr5-35860901-C-T
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_002185.5(IL7R):c.132C>T(p.Ser44=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000801 in 1,613,370 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★★).
Frequency
Genomes: 𝑓 0.0042 ( 6 hom., cov: 33)
Exomes 𝑓: 0.00045 ( 4 hom. )
Consequence
IL7R
NM_002185.5 synonymous
NM_002185.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.209
Genes affected
IL7R (HGNC:6024): (interleukin 7 receptor) The protein encoded by this gene is a receptor for interleukin 7 (IL7). The function of this receptor requires the interleukin 2 receptor, gamma chain (IL2RG), which is a common gamma chain shared by the receptors of various cytokines, including interleukins 2, 4, 7, 9, and 15. This protein has been shown to play a critical role in V(D)J recombination during lymphocyte development. Defects in this gene may be associated with severe combined immunodeficiency (SCID). Alternatively spliced transcript variants have been found. [provided by RefSeq, Dec 2015]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
Variant 5-35860901-C-T is Benign according to our data. Variant chr5-35860901-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 377976.Status of the report is reviewed_by_expert_panel, 3 stars.
BP7
?
Synonymous conserved (PhyloP=-0.209 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00418 (636/152212) while in subpopulation AFR AF= 0.0138 (573/41528). AF 95% confidence interval is 0.0129. There are 6 homozygotes in gnomad4. There are 298 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL7R | NM_002185.5 | c.132C>T | p.Ser44= | synonymous_variant | 2/8 | ENST00000303115.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL7R | ENST00000303115.8 | c.132C>T | p.Ser44= | synonymous_variant | 2/8 | 1 | NM_002185.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00418 AC: 635AN: 152094Hom.: 6 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
635
AN:
152094
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00117 AC: 294AN: 251166Hom.: 2 AF XY: 0.000869 AC XY: 118AN XY: 135746
GnomAD3 exomes
AF:
AC:
294
AN:
251166
Hom.:
AF XY:
AC XY:
118
AN XY:
135746
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000449 AC: 656AN: 1461158Hom.: 4 Cov.: 30 AF XY: 0.000410 AC XY: 298AN XY: 726910
GnomAD4 exome
AF:
AC:
656
AN:
1461158
Hom.:
Cov.:
30
AF XY:
AC XY:
298
AN XY:
726910
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00418 AC: 636AN: 152212Hom.: 6 Cov.: 33 AF XY: 0.00400 AC XY: 298AN XY: 74418
GnomAD4 genome
?
AF:
AC:
636
AN:
152212
Hom.:
Cov.:
33
AF XY:
AC XY:
298
AN XY:
74418
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
5
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:7
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Immunodeficiency 104 Benign:4
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 08, 2021 | - - |
Likely benign, reviewed by expert panel | curation | ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen | Nov 14, 2023 | The c.132C>T (p.Ser44=) variant (NM_002185.5) variant in IL7R is a synonymous (silent) variant that is not predicted to impact splicing (BP7). The filtering allele frequency (the lower threshold of the 95% CI of 342/24962) of the c.132C>T variant in IL7R is 0.01271 in exomes and 0.01082 in genomes for African/African American chromosomes by gnomAD v2.1.1. Both values are higher than the ClinGen SCID VCEP threshold (0.00126) for BS1 and therefore meet this criterion (BS1). In summary, this variant meets the criteria to be classified as likely benign for SCID. ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: BP7 and BS1. (VCEP specifications version 1). - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 21, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
IL7R-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 04, 2023 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | IL7R: BP4, BP7, BS1, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at