NM_002163.4:c.602-1337A>G

Variant names:

• chr16-85917080-A-G
• rs11117415
• NM_002163.4:c.602-1337A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002163.4(IRF8):​c.602-1337A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,174 control chromosomes in the GnomAD database, including 1,790 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 0.12 (1790 hom., cov: 32)
• Consequence: IRF8 NM_002163.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 8 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 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF8	NM_002163.4	MANE Select	c.602-1337A>G		intron	N/A	NP_002154.1	Q02556
	IRF8	NM_001363907.1		c.632-1337A>G		intron	N/A	NP_001350836.1
	IRF8	NM_001363908.1		c.-11-1337A>G		intron	N/A	NP_001350837.1	H3BRT4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF8	ENST00000268638.10	TSL:1 MANE Select	c.602-1337A>G		intron	N/A	ENSP00000268638.4	Q02556
	IRF8	ENST00000564803.6	TSL:2	c.602-1337A>G		intron	N/A	ENSP00000456992.2	Q02556
	IRF8	ENST00000696887.1		c.602-1337A>G		intron	N/A	ENSP00000512953.1	Q02556

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18587 AN: 152056 Hom.: 1785 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0632

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.0342

Gnomad FIN AF: 0.0597

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0519

Gnomad OTH AF: 0.128

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.122 AC: 18616 AN: 152174 Hom.: 1790 Cov.: 32 AF XY: 0.121 AC XY: 8966 AN XY: 74404

African (AFR) AF: 0.262 AC: 10874 AN: 41498

American (AMR) AF: 0.112 AC: 1713 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0632 AC: 219 AN: 3466

East Asian (EAS) AF: 0.218 AC: 1125 AN: 5172

South Asian (SAS) AF: 0.0347 AC: 167 AN: 4816

European-Finnish (FIN) AF: 0.0597 AC: 634 AN: 10622

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0519 AC: 3527 AN: 67984

Other (OTH) AF: 0.131 AC: 276 AN: 2114

Alfa AF: 0.0734 Hom.: 899

Bravo AF: 0.135

Asia WGS AF: 0.125 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.0
DANN	Benign	0.40
PhyloP100		-0.057
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

Other links and lift over

dbSNP: rs11117415; hg19: chr16-85950686;