rs11117415

Positions:

• chr16-85917080-A-G
• chr16-85917080-A-T

Variant summary

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

The NM_002163.4(IRF8):​c.602-1337A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,174 control chromosomes in the GnomAD database, including 1,790 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 0.12 (1790 hom., cov: 32)
• Consequence: IRF8 NM_002163.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF8	NM_002163.4	c.602-1337A>G		intron_variant		ENST00000268638.10
IRF8	NM_001363907.1	c.632-1337A>G		intron_variant
IRF8	NM_001363908.1	c.-11-1337A>G		intron_variant
IRF8	XM_047434052.1	c.632-1337A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF8	ENST00000268638.10	c.602-1337A>G		intron_variant		1	NM_002163.4	P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18587 AN: 152056 Hom.: 1785 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0632

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.0342

Gnomad FIN AF: 0.0597

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0519

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.122 AC: 18616 AN: 152174 Hom.: 1790 Cov.: 32 AF XY: 0.121 AC XY: 8966 AN XY: 74404

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0632

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.0347

Gnomad4 FIN AF: 0.0597

Gnomad4 NFE AF: 0.0519

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0624 Hom.: 445

Bravo AF: 0.135

Asia WGS AF: 0.125 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.0
DANN	Benign	0.40

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: rs11117415; hg19: chr16-85950686;