chr16-85921636-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002163.4(IRF8):c.*354C>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 0.219 in 279,678 control chromosomes in the GnomAD database, including 6,989 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 3935 hom., cov: 33)

Exomes 𝑓: 0.21 ( 3054 hom. )

Consequence

IRF8
NM_002163.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.506

Publications

20 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

IRF8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-85921636-C-T is Benign according to our data. Variant chr16-85921636-C-T is described in ClinVar as Benign. ClinVar VariationId is 1168174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IRF8	NM_002163.4 link	c.*354C>T	3_prime_UTR_variant	Exon 9 of 9	ENST00000268638.10	NP_002154.1	Q02556
IRF8	NM_001363907.1 link	c.*354C>T	3_prime_UTR_variant	Exon 9 of 9		NP_001350836.1
IRF8	NM_001363908.1 link	c.*354C>T	3_prime_UTR_variant	Exon 7 of 7		NP_001350837.1
IRF8	XM_047434052.1 link	c.*354C>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
IRF8	ENST00000268638.10 link	c.*354C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_002163.4	ENSP00000268638.4		Q02556

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34230

AN:

152012

Hom.:

3929

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.196

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.215

GnomAD4 exome

AF:

0.212

AC:

27001

AN:

127548

Hom.:

3054

Cov.:

AF XY:

0.205

AC XY:

13747

AN XY:

67134

show subpopulations

African (AFR)

AF:

0.235

AC:

892

AN:

3790

American (AMR)

AF:

0.181

AC:

863

AN:

4762

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

663

AN:

3500

East Asian (EAS)

AF:

0.211

AC:

1244

AN:

5900

South Asian (SAS)

AF:

0.138

AC:

2673

AN:

19334

European-Finnish (FIN)

AF:

0.305

AC:

1899

AN:

6218

Middle Eastern (MID)

AF:

0.131

AC:

AN:

512

European-Non Finnish (NFE)

AF:

0.224

AC:

17141

AN:

76606

Other (OTH)

AF:

0.225

AC:

1559

AN:

6926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1017

2034

3051

4068

5085

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

146

292

438

584

730

<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:

0.225

AC:

34268

AN:

152130

Hom.:

3935

Cov.:

AF XY:

0.226

AC XY:

16770

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.238

AC:

9875

AN:

41500

American (AMR)

AF:

0.179

AC:

2742

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

655

AN:

3468

East Asian (EAS)

AF:

0.197

AC:

1020

AN:

5184

South Asian (SAS)

AF:

0.126

AC:

607

AN:

4830

European-Finnish (FIN)

AF:

0.306

AC:

3225

AN:

10552

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.227

AC:

15459

AN:

67984

Other (OTH)

AF:

0.220

AC:

464

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1427

2855

4282

5710

7137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<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:

0.225

Hom.:

14574

Bravo

AF:

0.218

Asia WGS

AF:

0.176

AC:

612

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency;C4751209:Immunodeficiency 32B

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.6

(source)

DANN

Benign

0.56

PhyloP100

-0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over