rs2292980

chr16-85911470-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002163.4(IRF8):c.359-100T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,007,118 control chromosomes in the GnomAD database, including 64,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (11797 hom., cov: 33)
  • Exomes 𝑓: 0.35 (52618 hom.)
• Consequence: IRF8 NM_002163.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.25

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-85911470-T-C is Benign according to our data. Variant chr16-85911470-T-C is described in ClinVar as [Benign]. Clinvar id is 2688501.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF8	NM_002163.4	c.359-100T>C		intron_variant		ENST00000268638.10
IRF8	NM_001363907.1	c.389-100T>C		intron_variant
IRF8	NM_001363908.1	c.-148-100T>C		intron_variant
IRF8	XM_047434052.1	c.389-100T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF8	ENST00000268638.10	c.359-100T>C		intron_variant		1	NM_002163.4	P1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58801 AN: 151968 Hom.: 11748 Cov.: 33

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.346 AC: 296166 AN: 855032 Hom.: 52618 AF XY: 0.343 AC XY: 152402 AN XY: 444618

Gnomad4 AFR exome AF: 0.485

Gnomad4 AMR exome AF: 0.361

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.434

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.395

Gnomad4 NFE exome AF: 0.339

Gnomad4 OTH exome AF: 0.373

GnomAD4 genome AF: 0.387 AC: 58901 AN: 152086 Hom.: 11797 Cov.: 33 AF XY: 0.387 AC XY: 28783 AN XY: 74346

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.402

Alfa AF: 0.370 Hom.: 2167

Bravo AF: 0.391

Asia WGS AF: 0.411 AC: 1425 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 22% of patients studied by a panel of primary immunodeficiencies. Number of patients: 19. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.26
Dann	Benign	0.37

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: rs2292980; hg19: chr16-85945076; COSMIC: COSV51897129; COSMIC: COSV51897129;