rs375419913
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_005534.4(IFNGR2):āc.514T>Gā(p.Phe172Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,611,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F172I) has been classified as Uncertain significance.
Frequency
Consequence
NM_005534.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFNGR2 | NM_005534.4 | c.514T>G | p.Phe172Val | missense_variant | 4/7 | ENST00000290219.11 | |
IFNGR2 | NM_001329128.2 | c.571T>G | p.Phe191Val | missense_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFNGR2 | ENST00000290219.11 | c.514T>G | p.Phe172Val | missense_variant | 4/7 | 1 | NM_005534.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152032Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251326Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135806
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1459048Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726010
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152032Hom.: 0 Cov.: 30 AF XY: 0.0000404 AC XY: 3AN XY: 74262
ClinVar
Submissions by phenotype
Immunodeficiency 28 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 18, 2022 | This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 172 of the IFNGR2 protein (p.Phe172Val). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with IFNGR2-related conditions. This variant is present in population databases (rs375419913, gnomAD 0.01%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at