rs771773479
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_002163.4(IRF8):c.1081C>A(p.Arg361Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000714 in 1,400,420 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R361G) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )
Consequence
IRF8
NM_002163.4 missense
NM_002163.4 missense
Scores
12
6
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.45
Publications
0 publications found
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]
IRF8 Gene-Disease associations (from GenCC):
- Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiencyInheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Illumina
- immunodeficiency 32BInheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_002163.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| IRF8 | NM_002163.4 | MANE Select | c.1081C>A | p.Arg361Ser | missense | Exon 8 of 9 | NP_002154.1 | ||
| IRF8 | NM_001363907.1 | c.1111C>A | p.Arg371Ser | missense | Exon 8 of 9 | NP_001350836.1 | |||
| IRF8 | NM_001363908.1 | c.469C>A | p.Arg157Ser | missense | Exon 6 of 7 | NP_001350837.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| IRF8 | ENST00000268638.10 | TSL:1 MANE Select | c.1081C>A | p.Arg361Ser | missense | Exon 8 of 9 | ENSP00000268638.4 | ||
| IRF8 | ENST00000566369.2 | TSL:3 | c.540C>A | p.Cys180* | stop_gained | Exon 5 of 6 | ENSP00000455048.2 | ||
| IRF8 | ENST00000564803.6 | TSL:2 | c.1081C>A | p.Arg361Ser | missense | Exon 8 of 9 | ENSP00000456992.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 7.14e-7 AC: 1AN: 1400420Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 698896 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1400420
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
698896
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
32180
American (AMR)
AF:
AC:
0
AN:
44306
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25360
East Asian (EAS)
AF:
AC:
0
AN:
38374
South Asian (SAS)
AF:
AC:
0
AN:
85296
European-Finnish (FIN)
AF:
AC:
0
AN:
52354
Middle Eastern (MID)
AF:
AC:
0
AN:
5566
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1059028
Other (OTH)
AF:
AC:
0
AN:
57956
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
PhyloP100
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MutPred
Gain of ubiquitination at K363 (P = 0.0747)
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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