16-85904050-C-G

Variant names:

• chr16-85904050-C-G
• rs182511
• NM_002163.4:c.174+861C>G

Variant summary

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

The NM_001363907.1(IRF8):​c.204+861C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0846 in 152,256 control chromosomes in the GnomAD database, including 1,382 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 0.085 (1382 hom., cov: 32)
• Consequence: IRF8 NM_001363907.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363907.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF8	NM_002163.4	MANE Select	c.174+861C>G		intron	N/A	NP_002154.1
	IRF8	NM_001363907.1		c.204+861C>G		intron	N/A	NP_001350836.1
	IRF8	NM_001363908.1		c.-333+861C>G		intron	N/A	NP_001350837.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF8	ENST00000268638.10	TSL:1 MANE Select	c.174+861C>G		intron	N/A	ENSP00000268638.4
	IRF8	ENST00000563180.1	TSL:1	c.174+861C>G		intron	N/A	ENSP00000458047.1
	IRF8	ENST00000564803.6	TSL:2	c.174+861C>G		intron	N/A	ENSP00000456992.2

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12868 AN: 152138 Hom.: 1377 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0833

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

GnomAD4 genome AF: 0.0846 AC: 12887 AN: 152256 Hom.: 1382 Cov.: 32 AF XY: 0.0917 AC XY: 6828 AN XY: 74438

African (AFR) AF: 0.107 AC: 4444 AN: 41538

American (AMR) AF: 0.236 AC: 3604 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 180 AN: 3468

East Asian (EAS) AF: 0.413 AC: 2133 AN: 5170

South Asian (SAS) AF: 0.182 AC: 876 AN: 4822

European-Finnish (FIN) AF: 0.0193 AC: 205 AN: 10618

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0180 AC: 1225 AN: 68040

Other (OTH) AF: 0.0820 AC: 173 AN: 2110

Alfa AF: 0.00527 Hom.: 3

Bravo AF: 0.102

Asia WGS AF: 0.275 AC: 956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.37
PhyloP100		-0.32
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: rs182511; hg19: chr16-85937656;