16-85920150-G-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_002163.4(IRF8):c.1030G>T(p.Gly344Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002163.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IRF8 | NM_002163.4 | c.1030G>T | p.Gly344Cys | missense_variant | Exon 8 of 9 | ENST00000268638.10 | NP_002154.1 | |
IRF8 | NM_001363907.1 | c.1060G>T | p.Gly354Cys | missense_variant | Exon 8 of 9 | NP_001350836.1 | ||
IRF8 | NM_001363908.1 | c.418G>T | p.Gly140Cys | missense_variant | Exon 6 of 7 | NP_001350837.1 | ||
IRF8 | XM_047434052.1 | c.1060G>T | p.Gly354Cys | missense_variant | Exon 9 of 10 | XP_047290008.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461862Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727238
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency;C4016741:Immunodeficiency 32B Uncertain:1
This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 344 of the IRF8 protein (p.Gly344Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with IRF8-related conditions. ClinVar contains an entry for this variant (Variation ID: 1415198). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt IRF8 protein function with a negative predictive value of 80%. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at