rs13338943

Variant names:

• chr16-85919345-G-T
• rs13338943
• NM_002163.4:c.988+542G>T

Variant summary

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

The NM_002163.4(IRF8):​c.988+542G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,142 control chromosomes in the GnomAD database, including 1,146 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 (1146 hom., cov: 33)
• Consequence: IRF8 NM_002163.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 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.988+542G>T		intron	N/A	NP_002154.1	Q02556
	IRF8	NM_001363907.1		c.1018+542G>T		intron	N/A	NP_001350836.1
	IRF8	NM_001363908.1		c.376+542G>T		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.988+542G>T		intron	N/A	ENSP00000268638.4	Q02556
	IRF8	ENST00000564803.6	TSL:2	c.988+542G>T		intron	N/A	ENSP00000456992.2	Q02556
	IRF8	ENST00000696887.1		c.988+542G>T		intron	N/A	ENSP00000512953.1	Q02556

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17657 AN: 152024 Hom.: 1143 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.0973

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0750

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.0590

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.116 AC: 17672 AN: 152142 Hom.: 1146 Cov.: 33 AF XY: 0.113 AC XY: 8417 AN XY: 74394

African (AFR) AF: 0.152 AC: 6295 AN: 41484

American (AMR) AF: 0.0973 AC: 1489 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3470

East Asian (EAS) AF: 0.0747 AC: 386 AN: 5164

South Asian (SAS) AF: 0.0885 AC: 427 AN: 4826

European-Finnish (FIN) AF: 0.0590 AC: 626 AN: 10612

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7368 AN: 67976

Other (OTH) AF: 0.128 AC: 270 AN: 2110

Alfa AF: 0.113 Hom.: 1435

Bravo AF: 0.123

Asia WGS AF: 0.0860 AC: 300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		-0.19
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: rs13338943; hg19: chr16-85952951;