chr16-85922065-C-T

Position:

• chr16-85922065-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002163.4(IRF8):​c.*783C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,172 control chromosomes in the GnomAD database, including 12,308 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 0.40 (12292 hom., cov: 33)
  • Exomes 𝑓: 0.38 (16 hom.)
• Consequence: IRF8 NM_002163.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF8	NM_002163.4	c.*783C>T		3_prime_UTR_variant	9/9	ENST00000268638.10	NP_002154.1
IRF8	NM_001363907.1	c.*783C>T		3_prime_UTR_variant	9/9		NP_001350836.1
IRF8	NM_001363908.1	c.*783C>T		3_prime_UTR_variant	7/7		NP_001350837.1
IRF8	XM_047434052.1	c.*783C>T		3_prime_UTR_variant	10/10		XP_047290008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF8	ENST00000268638.10	c.*783C>T		3_prime_UTR_variant	9/9	1	NM_002163.4	ENSP00000268638.4

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60291 AN: 151896 Hom.: 12261 Cov.: 33

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.386

GnomAD4 exome AF: 0.380 AC: 60 AN: 158 Hom.: 16 Cov.: 0 AF XY: 0.386 AC XY: 34 AN XY: 88

Gnomad4 EAS exome AF: 0.404

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.397 AC: 60376 AN: 152014 Hom.: 12292 Cov.: 33 AF XY: 0.396 AC XY: 29384 AN XY: 74284

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.393

Alfa AF: 0.382 Hom.: 22919

Bravo AF: 0.390

Asia WGS AF: 0.350 AC: 1216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.73

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: rs1044873; hg19: chr16-85955671;