dbSNP rs1555610239: IRF8:c.-233_-224dupTGGTGGCTGC (chr16-85902776-G-GGGCTGCTGGT) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_002163.4(IRF8):c.-1-232_-1-223dupTGGTGGCTGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 354,178 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000012 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

IRF8
NM_002163.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.626

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 16-85902776-G-GGGCTGCTGGT is Benign according to our data. Variant chr16-85902776-G-GGGCTGCTGGT is described in ClinVar as [Benign]. Clinvar id is 2688451.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IRF8	NM_002163.4 link	c.-1-232_-1-223dupTGGTGGCTGC	intron_variant	Intron 1 of 8	ENST00000268638.10	NP_002154.1	Q02556
IRF8	XM_047434052.1 link	c.-78_-69dupTGGTGGCTGC	5_prime_UTR_variant	Exon 2 of 10		XP_047290008.1
IRF8	NM_001363907.1 link	c.-85_-84insGGCTGCTGGT	upstream_gene_variant			NP_001350836.1
IRF8	NM_001363908.1 link	c.-746_-745insGGCTGCTGGT	upstream_gene_variant			NP_001350837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF8	ENST00000268638.10 link	c.-1-232_-1-223dupTGGTGGCTGC		intron_variant	Intron 1 of 8	1	NM_002163.4	ENSP00000268638.4		Q02556

Frequencies

GnomAD3 genomes

AF:

0.0000123

AC:

AN:

81356

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000206

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000183

AC:

AN:

272822

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

146588

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

5416

American (AMR)

AF:

0.00

AC:

AN:

11414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8206

East Asian (EAS)

AF:

0.00

AC:

AN:

10904

South Asian (SAS)

AF:

0.00

AC:

AN:

35892

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1092

European-Non Finnish (NFE)

AF:

0.0000235

AC:

AN:

170114

Other (OTH)

AF:

0.0000686

AC:

AN:

14572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000123

AC:

AN:

81356

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

39130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

9800

American (AMR)

AF:

0.00

AC:

AN:

7316

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2388

East Asian (EAS)

AF:

0.00

AC:

AN:

1578

South Asian (SAS)

AF:

0.00

AC:

AN:

2876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6830

Middle Eastern (MID)

AF:

0.00

AC:

AN:

204

European-Non Finnish (NFE)

AF:

0.0000206

AC:

AN:

48648

Other (OTH)

AF:

0.00

AC:

AN:

1124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 34% of patients studied by a panel of primary immunodeficiencies. Number of patients: 30. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.63

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over