Variant rs61995933 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The ENST00000268638.10(IRF8):c.894C>T(p.Phe298=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00708 in 1,612,538 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0073 ( 47 hom. )

Consequence

IRF8
ENST00000268638.10 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.45

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 16-85918709-C-T is Benign according to our data. Variant chr16-85918709-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 542149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.45 with no splicing effect.

BS2

High AC in GnomAd4 at 811 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IRF8	NM_002163.4 linkuse as main transcript	c.894C>T	p.Phe298=	synonymous_variant	7/9	ENST00000268638.10	NP_002154.1
IRF8	NM_001363907.1 linkuse as main transcript	c.924C>T	p.Phe308=	synonymous_variant	7/9		NP_001350836.1
IRF8	NM_001363908.1 linkuse as main transcript	c.282C>T	p.Phe94=	synonymous_variant	5/7		NP_001350837.1
IRF8	XM_047434052.1 linkuse as main transcript	c.924C>T	p.Phe308=	synonymous_variant	8/10		XP_047290008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF8	ENST00000268638.10 linkuse as main transcript	c.894C>T	p.Phe298=	synonymous_variant	7/9	1	NM_002163.4	ENSP00000268638	P1

Frequencies

GnomAD3 genomes

AF:

0.00533

AC:

811

AN:

152286

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00903

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00861

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00528

AC:

1312

AN:

248584

Hom.:

AF XY:

0.00531

AC XY:

716

AN XY:

134916

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.000499

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000556

Gnomad FIN exome

AF:

0.00951

Gnomad NFE exome

AF:

0.00873

Gnomad OTH exome

AF:

0.00576

GnomAD4 exome

AF:

0.00726

AC:

10603

AN:

1460134

Hom.:

Cov.:

AF XY:

0.00714

AC XY:

5188

AN XY:

726478

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00159

Gnomad4 ASJ exome

AF:

0.000880

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000649

Gnomad4 FIN exome

AF:

0.00904

Gnomad4 NFE exome

AF:

0.00862

Gnomad4 OTH exome

AF:

0.00565

GnomAD4 genome

AF:

0.00532

AC:

811

AN:

152404

Hom.:

Cov.:

AF XY:

0.00490

AC XY:

365

AN XY:

74532

show subpopulations

Gnomad4 AFR

AF:

0.00185

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00903

Gnomad4 NFE

AF:

0.00861

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00645

Hom.:

Bravo

AF:

0.00449

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00731

EpiControl

AF:

0.00824

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	IRF8: BP4, BP7, BS2 -

Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency;C4016741:Immunodeficiency 32B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

IRF8-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 06, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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