dbSNP rs305077: IRF8:c.*664T>C (chr16-85909860-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000563180.1(IRF8):c.*664T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,462 control chromosomes in the GnomAD database, including 13,795 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 0.41 ( 13787 hom., cov: 33)

Exomes 𝑓: 0.23 ( 8 hom. )

Consequence

IRF8
ENST00000563180.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.831

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

IRF8 links:

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 (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IRF8	NM_002163.4 link	c.358+687T>C	intron_variant	Intron 3 of 8	ENST00000268638.10	NP_002154.1	Q02556
IRF8	NM_001363907.1 link	c.388+687T>C	intron_variant	Intron 3 of 8		NP_001350836.1
IRF8	NM_001363908.1 link	c.-149+687T>C	intron_variant	Intron 2 of 6		NP_001350837.1
IRF8	XM_047434052.1 link	c.388+687T>C	intron_variant	Intron 4 of 9		XP_047290008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF8	ENST00000268638.10 link	c.358+687T>C		intron_variant	Intron 3 of 8	1	NM_002163.4	ENSP00000268638.4		Q02556

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

62074

AN:

152006

Hom.:

13745

Cov.:

show subpopulations

Gnomad AFR

AF:

0.594

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.301

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.401

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.409

GnomAD4 exome

AF:

0.228

AC:

AN:

338

Hom.:

Cov.:

AF XY:

0.208

AC XY:

AN XY:

168

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.0769

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.232

AC:

AN:

302

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.409

AC:

62167

AN:

152124

Hom.:

13787

Cov.:

AF XY:

0.407

AC XY:

30261

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.595

AC:

24671

AN:

41472

American (AMR)

AF:

0.309

AC:

4715

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

1196

AN:

3472

East Asian (EAS)

AF:

0.300

AC:

1558

AN:

5192

South Asian (SAS)

AF:

0.258

AC:

1246

AN:

4828

European-Finnish (FIN)

AF:

0.401

AC:

4244

AN:

10584

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.343

AC:

23301

AN:

67982

Other (OTH)

AF:

0.411

AC:

868

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1800

3599

5399

7198

8998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

572

1144

1716

2288

2860

<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:

0.414

Hom.:

3722

Bravo

AF:

0.413

Asia WGS

AF:

0.342

AC:

1185

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

0.21

(source)

DANN

Benign

0.17

PhyloP100

-0.83

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

Computational scores

Splicing

Publications

Other links and lift over