16-85912875-G-C

Variant names:

• chr16-85912875-G-C
• rs11649318
• NM_002163.4:c.448-256G>C

Variant summary

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

The NM_002163.4(IRF8):​c.448-256G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,088 control chromosomes in the GnomAD database, including 14,162 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 0.42 (14162 hom., cov: 33)
• Consequence: IRF8 NM_002163.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF8	NM_002163.4	c.448-256G>C		intron_variant	Intron 4 of 8	ENST00000268638.10	NP_002154.1
IRF8	NM_001363907.1	c.478-256G>C		intron_variant	Intron 4 of 8		NP_001350836.1
IRF8	NM_001363908.1	c.-60+1217G>C		intron_variant	Intron 3 of 6		NP_001350837.1
IRF8	XM_047434052.1	c.478-256G>C		intron_variant	Intron 5 of 9		XP_047290008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF8	ENST00000268638.10	c.448-256G>C		intron_variant	Intron 4 of 8	1	NM_002163.4	ENSP00000268638.4

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64235 AN: 151970 Hom.: 14118 Cov.: 33

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.423 AC: 64333 AN: 152088 Hom.: 14162 Cov.: 33 AF XY: 0.421 AC XY: 31327 AN XY: 74346

African (AFR) AF: 0.543 AC: 22515 AN: 41488

American (AMR) AF: 0.333 AC: 5090 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1198 AN: 3470

East Asian (EAS) AF: 0.426 AC: 2210 AN: 5184

South Asian (SAS) AF: 0.284 AC: 1366 AN: 4814

European-Finnish (FIN) AF: 0.438 AC: 4633 AN: 10586

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 25991 AN: 67948

Other (OTH) AF: 0.435 AC: 919 AN: 2114

Alfa AF: 0.251 Hom.: 559

Bravo AF: 0.423

Asia WGS AF: 0.399 AC: 1385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.72
PhyloP100		0.31
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

Publications

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Other links and lift over

dbSNP: rs11649318; hg19: chr16-85946481;