16-85912875-G-C

Position:

• chr16-85912875-G-C

Variant summary

Our verdict is Benign. Variant got -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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
IRF8	NM_002163.4	c.448-256G>C		intron_variant		ENST00000268638.10
IRF8	NM_001363907.1	c.478-256G>C		intron_variant
IRF8	NM_001363908.1	c.-60+1217G>C		intron_variant
IRF8	XM_047434052.1	c.478-256G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF8	ENST00000268638.10	c.448-256G>C		intron_variant		1	NM_002163.4	P1

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

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.435

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

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

LitVar

Other links and lift over

dbSNP: rs11649318; hg19: chr16-85946481;