NM_002163.4:c.602-227T>G

Variant names:

• chr16-85918190-T-G
• rs8064189
• NM_002163.4:c.602-227T>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.602-227T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,062 control chromosomes in the GnomAD database, including 9,933 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 0.34 (9933 hom., cov: 33)
• Consequence: IRF8 NM_002163.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890
• 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]

MIR6774 (HGNC:50202): (microRNA 6774) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

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 (EAS) allele frequency at 95% confidence interval = 0.519 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF8	NM_002163.4	MANE Select	c.602-227T>G		intron	N/A	NP_002154.1
	IRF8	NM_001363907.1		c.632-227T>G		intron	N/A	NP_001350836.1
	IRF8	NM_001363908.1		c.-11-227T>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.602-227T>G		intron	N/A	ENSP00000268638.4
	IRF8	ENST00000564803.6	TSL:2	c.602-227T>G		intron	N/A	ENSP00000456992.2
	IRF8	ENST00000696887.1		c.602-227T>G		intron	N/A	ENSP00000512953.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52113 AN: 151944 Hom.: 9897 Cov.: 33

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.343 AC: 52205 AN: 152062 Hom.: 9933 Cov.: 33 AF XY: 0.349 AC XY: 25951 AN XY: 74322

African (AFR) AF: 0.462 AC: 19166 AN: 41462

American (AMR) AF: 0.464 AC: 7089 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 778 AN: 3472

East Asian (EAS) AF: 0.536 AC: 2760 AN: 5154

South Asian (SAS) AF: 0.320 AC: 1540 AN: 4820

European-Finnish (FIN) AF: 0.314 AC: 3323 AN: 10576

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.244 AC: 16595 AN: 67986

Other (OTH) AF: 0.327 AC: 691 AN: 2110

Alfa AF: 0.233 Hom.: 886

Bravo AF: 0.359

Asia WGS AF: 0.454 AC: 1576 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	6.9
DANN	Benign	0.75
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs8064189; hg19: chr16-85951796;