rs141548724
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_002163.4(IRF8):c.1131G>A(p.Leu377=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
IRF8
NM_002163.4 synonymous
NM_002163.4 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 2.94
Genes affected
IRF8 (HGNC:5358): (interferon regulatory factor 8) Interferon consensus sequence-binding protein (ICSBP) is a transcription factor of the interferon (IFN) regulatory factor (IRF) family. Proteins of this family are composed of a conserved DNA-binding domain in the N-terminal region and a divergent C-terminal region that serves as the regulatory domain. The IRF family proteins bind to the IFN-stimulated response element (ISRE) and regulate expression of genes stimulated by type I IFNs, namely IFN-alpha and IFN-beta. IRF family proteins also control expression of IFN-alpha and IFN-beta-regulated genes that are induced by viral infection. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 16-85921132-G-A is Benign according to our data. Variant chr16-85921132-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 571600.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=2.94 with no splicing effect.
BS2
?
High AC in GnomAd4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IRF8 | NM_002163.4 | c.1131G>A | p.Leu377= | synonymous_variant | 9/9 | ENST00000268638.10 | |
IRF8 | NM_001363907.1 | c.1161G>A | p.Leu387= | synonymous_variant | 9/9 | ||
IRF8 | NM_001363908.1 | c.519G>A | p.Leu173= | synonymous_variant | 7/7 | ||
IRF8 | XM_047434052.1 | c.1161G>A | p.Leu387= | synonymous_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IRF8 | ENST00000268638.10 | c.1131G>A | p.Leu377= | synonymous_variant | 9/9 | 1 | NM_002163.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152228Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000320 AC: 8AN: 249916Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135290
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461642Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727120
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152228Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74370
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency;C4016741:Immunodeficiency 32B Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at