rs148104171
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_000416.3(IFNGR1):c.135C>T(p.Ile45=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,613,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
IFNGR1
NM_000416.3 synonymous
NM_000416.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.491
Genes affected
IFNGR1 (HGNC:5439): (interferon gamma receptor 1) This gene (IFNGR1) encodes the ligand-binding chain (alpha) of the gamma interferon receptor. Human interferon-gamma receptor is a heterodimer of IFNGR1 and IFNGR2. A genetic variation in IFNGR1 is associated with susceptibility to Helicobacter pylori infection. In addition, defects in IFNGR1 are a cause of mendelian susceptibility to mycobacterial disease, also known as familial disseminated atypical mycobacterial infection. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 6-137207028-G-A is Benign according to our data. Variant chr6-137207028-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 495868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.491 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000115 (168/1461672) while in subpopulation EAS AF= 0.00227 (90/39662). AF 95% confidence interval is 0.00189. There are 0 homozygotes in gnomad4_exome. There are 85 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFNGR1 | NM_000416.3 | c.135C>T | p.Ile45= | synonymous_variant | 2/7 | ENST00000367739.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFNGR1 | ENST00000367739.9 | c.135C>T | p.Ile45= | synonymous_variant | 2/7 | 1 | NM_000416.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152168Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251386Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135862
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GnomAD4 exome AF: 0.000115 AC: 168AN: 1461672Hom.: 0 Cov.: 30 AF XY: 0.000117 AC XY: 85AN XY: 727148
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74332
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Disseminated atypical mycobacterial infection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 13, 2017 | Variant summary: The IFNGR1 c.135C>T (p.Ile45Ile) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation Taster predicts a benign outcome for this variant. 5/5 splice prediction tools also predict no significant impact on normal splicing. This variant was found in 27/121914 control chromosomes at a frequency of 0.0002215, which does not exceed the estimated maximal expected allele frequency of a pathogenic IFNGR1 variant (0.001118) under recessive module. However, it was found in allele frequency of 4% in 282 randomly selected, population-based individuals 19 to 68 years of age (mean, 38.21) with no atopy-related diseases from Japan (Matsuda_2007); thus it is a polymorphism mainly found in Japanese population. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases. Taken together, this variant is classified as Benign. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at