rs786205223
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001572.5(IRF7):c.1228T>G(p.Phe410Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000418 in 1,436,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F410L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001572.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IRF7 | NM_001572.5 | c.1228T>G | p.Phe410Val | missense_variant | 9/11 | ENST00000525445.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IRF7 | ENST00000525445.6 | c.1228T>G | p.Phe410Val | missense_variant | 9/11 | 5 | NM_001572.5 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000418 AC: 6AN: 1436234Hom.: 0 Cov.: 41 AF XY: 0.00000140 AC XY: 1AN XY: 712284
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Immunodeficiency 39 Pathogenic:1Uncertain:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 24, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 28, 2022 | 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. Experimental studies have shown that this missense change affects IRF7 function (PMID: 25814066). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 190237). This variant is also known as F410V. This missense change has been observed in individual(s) with IRF7 deficiency (PMID: 25814066). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 423 of the IRF7 protein (p.Phe423Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at