Variant rs2292980 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.25

Variant links:

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 links:

IRF8 (HGNC:):

IRF8 links:

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ACMG classification

Classification made for transcript

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	Effect	MANE	Protein	UniProt
IRF8	NM_002163.4 linkuse as main transcript	c.359-100T>C	intron_variant	ENST00000268638.10	NP_002154.1	Q02556
IRF8	NM_001363907.1 linkuse as main transcript	c.389-100T>C	intron_variant		NP_001350836.1
IRF8	NM_001363908.1 linkuse as main transcript	c.-148-100T>C	intron_variant		NP_001350837.1
IRF8	XM_047434052.1 linkuse as main transcript	c.389-100T>C	intron_variant		XP_047290008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF8	ENST00000268638.10 linkuse as main transcript	c.359-100T>C		intron_variant		1	NM_002163.4	ENSP00000268638.4		Q02556

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58801

AN:

151968

Hom.:

11748

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.387

AC XY:

28783

AN XY:

74346

show subpopulations

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

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over