16-85922438-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002163.4(IRF8):​c.*1156A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,200 control chromosomes in the GnomAD database, including 27,686 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.59 ( 27669 hom., cov: 32)
Exomes 𝑓: 0.50 ( 17 hom. )

Consequence

IRF8
NM_002163.4 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.597

Publications

12 publications found
Variant links:
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 deficiency
    Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Illumina
  • immunodeficiency 32B
    Inheritance: 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: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IRF8NM_002163.4 linkc.*1156A>T 3_prime_UTR_variant Exon 9 of 9 ENST00000268638.10 NP_002154.1 Q02556
IRF8NM_001363907.1 linkc.*1156A>T 3_prime_UTR_variant Exon 9 of 9 NP_001350836.1
IRF8NM_001363908.1 linkc.*1156A>T 3_prime_UTR_variant Exon 7 of 7 NP_001350837.1
IRF8XM_047434052.1 linkc.*1156A>T 3_prime_UTR_variant Exon 10 of 10 XP_047290008.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IRF8ENST00000268638.10 linkc.*1156A>T 3_prime_UTR_variant Exon 9 of 9 1 NM_002163.4 ENSP00000268638.4 Q02556

Frequencies

GnomAD3 genomes
AF:
0.593
AC:
90124
AN:
151944
Hom.:
27616
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.692
Gnomad AMI
AF:
0.643
Gnomad AMR
AF:
0.685
Gnomad ASJ
AF:
0.518
Gnomad EAS
AF:
0.855
Gnomad SAS
AF:
0.501
Gnomad FIN
AF:
0.550
Gnomad MID
AF:
0.560
Gnomad NFE
AF:
0.509
Gnomad OTH
AF:
0.597
GnomAD4 exome
AF:
0.500
AC:
69
AN:
138
Hom.:
17
Cov.:
0
AF XY:
0.513
AC XY:
40
AN XY:
78
show subpopulations
African (AFR)
AC:
0
AN:
0
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AF:
0.507
AC:
69
AN:
136
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
2
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AC:
0
AN:
0
Other (OTH)
AC:
0
AN:
0
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.474
Heterozygous variant carriers
0
2
4
6
8
10
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.593
AC:
90237
AN:
152062
Hom.:
27669
Cov.:
32
AF XY:
0.596
AC XY:
44333
AN XY:
74340
show subpopulations
African (AFR)
AF:
0.692
AC:
28708
AN:
41468
American (AMR)
AF:
0.686
AC:
10487
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.518
AC:
1797
AN:
3470
East Asian (EAS)
AF:
0.855
AC:
4429
AN:
5182
South Asian (SAS)
AF:
0.502
AC:
2416
AN:
4814
European-Finnish (FIN)
AF:
0.550
AC:
5801
AN:
10548
Middle Eastern (MID)
AF:
0.561
AC:
165
AN:
294
European-Non Finnish (NFE)
AF:
0.509
AC:
34581
AN:
67976
Other (OTH)
AF:
0.601
AC:
1268
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1819
3638
5458
7277
9096
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
744
1488
2232
2976
3720
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.418
Hom.:
1278
Bravo
AF:
0.613
Asia WGS
AF:
0.711
AC:
2471
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.18
DANN
Benign
0.41
PhyloP100
-0.60
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs6638; hg19: chr16-85956044; API