rs142267779
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_002163.4(IRF8):āc.724T>Cā(p.Tyr242His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00309 in 1,602,264 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0019 ( 0 hom., cov: 33)
Exomes š: 0.0032 ( 9 hom. )
Consequence
IRF8
NM_002163.4 missense
NM_002163.4 missense
Scores
2
10
7
Clinical Significance
Conservation
PhyloP100: 3.01
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 -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.032372504).
BP6
?
Variant 16-85918539-T-C is Benign according to our data. Variant chr16-85918539-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 542152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-85918539-T-C is described in Lovd as [Likely_benign].
BS2
?
High AC in GnomAd4 at 291 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IRF8 | NM_002163.4 | c.724T>C | p.Tyr242His | missense_variant | 7/9 | ENST00000268638.10 | |
IRF8 | NM_001363907.1 | c.754T>C | p.Tyr252His | missense_variant | 7/9 | ||
IRF8 | NM_001363908.1 | c.112T>C | p.Tyr38His | missense_variant | 5/7 | ||
IRF8 | XM_047434052.1 | c.754T>C | p.Tyr252His | missense_variant | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IRF8 | ENST00000268638.10 | c.724T>C | p.Tyr242His | missense_variant | 7/9 | 1 | NM_002163.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00191 AC: 291AN: 152214Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00188 AC: 445AN: 236408Hom.: 2 AF XY: 0.00186 AC XY: 242AN XY: 129950
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GnomAD4 exome AF: 0.00321 AC: 4658AN: 1449932Hom.: 9 Cov.: 31 AF XY: 0.00318 AC XY: 2293AN XY: 721566
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GnomAD4 genome ? AF: 0.00191 AC: 291AN: 152332Hom.: 0 Cov.: 33 AF XY: 0.00175 AC XY: 130AN XY: 74494
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ESP6500AA
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ExAC
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | IRF8: BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency;C4016741:Immunodeficiency 32B Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Uncertain
Sift
Benign
D;D;D;D
Sift4G
Benign
T;T;D;T
Polyphen
D;.;.;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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