rs774453718
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001098629.3(IRF5):c.248C>T(p.Pro83Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,262 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 (★).
Frequency
Consequence
NM_001098629.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250316Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135350
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461034Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726850
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74374
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: IRF5 c.248C>T (p.Pro83Leu) results in a non-conservative amino acid change located in the DNA-binding domain (IPR001346) of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250316 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.248C>T in individuals affected with IRF5-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at