16-85917315-A-G

Position:

• chr16-85917315-A-G

Variant summary

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

The ENST00000268638.10(IRF8):​c.602-1102A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,118 control chromosomes in the GnomAD database, including 4,200 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 0.22 (4200 hom., cov: 32)
• Consequence: IRF8 ENST00000268638.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.30

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF8	NM_002163.4	c.602-1102A>G		intron_variant		ENST00000268638.10	NP_002154.1
IRF8	NM_001363907.1	c.632-1102A>G		intron_variant			NP_001350836.1
IRF8	NM_001363908.1	c.-11-1102A>G		intron_variant			NP_001350837.1
IRF8	XM_047434052.1	c.632-1102A>G		intron_variant			XP_047290008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF8	ENST00000268638.10	c.602-1102A>G		intron_variant		1	NM_002163.4	ENSP00000268638	P1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34201 AN: 152000 Hom.: 4198 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.225 AC: 34212 AN: 152118 Hom.: 4200 Cov.: 32 AF XY: 0.223 AC XY: 16592 AN XY: 74370

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.267

Alfa AF: 0.258 Hom.: 8517

Bravo AF: 0.223

Asia WGS AF: 0.267 AC: 928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.74

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: rs4843860; hg19: chr16-85950921;