rs104893974
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP3_StrongPP5
The ENST00000367739.9(IFNGR1):c.230G>A(p.Cys77Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C77F) has been classified as Likely pathogenic.
Frequency
Genomes: not found (cov: 32)
Consequence
IFNGR1
ENST00000367739.9 missense
ENST00000367739.9 missense
Scores
10
7
2
Clinical Significance
Conservation
PhyloP100: 4.10
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 Pathogenic. Variant got 11 ACMG points.
PM1
In a disulfide_bond (size 8) in uniprot entity INGR1_HUMAN there are 6 pathogenic changes around while only 0 benign (100%) in ENST00000367739.9
PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.987
PP5
Variant 6-137206279-C-T is Pathogenic according to our data. Variant chr6-137206279-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 17949.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-137206279-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IFNGR1 | NM_000416.3 | c.230G>A | p.Cys77Tyr | missense_variant | 3/7 | ENST00000367739.9 | NP_000407.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IFNGR1 | ENST00000367739.9 | c.230G>A | p.Cys77Tyr | missense_variant | 3/7 | 1 | NM_000416.3 | ENSP00000356713 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 28
GnomAD4 exome
Cov.:
28
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Immunodeficiency 27A Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2000 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;.;.;.;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T;.;.;T;T;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.;.;.;.;.;.
MutationTaster
Benign
A;A
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;.;.;.;.;.;D
REVEL
Pathogenic
Sift
Pathogenic
D;.;.;.;.;.;.;D
Sift4G
Pathogenic
D;.;.;.;.;.;.;.
Polyphen
D;.;.;.;.;.;.;.
Vest4
MutPred
Loss of stability (P = 0.0223);.;.;.;.;.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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