16-85911625-C-T

Position:

chr16-85911625-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002163.4(IRF8):c.414C>T(p.Cys138=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,613,544 control chromosomes in the GnomAD database, including 15,197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1382 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13815 hom. )

Consequence

IRF8
NM_002163.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.575

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 16-85911625-C-T is Benign according to our data. Variant chr16-85911625-C-T is described in ClinVar as [Benign]. Clinvar id is 1168657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.575 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IRF8	NM_002163.4 linkuse as main transcript	c.414C>T	p.Cys138=	synonymous_variant	4/9	ENST00000268638.10	NP_002154.1
IRF8	NM_001363907.1 linkuse as main transcript	c.444C>T	p.Cys148=	synonymous_variant	4/9		NP_001350836.1
IRF8	XM_047434052.1 linkuse as main transcript	c.444C>T	p.Cys148=	synonymous_variant	5/10		XP_047290008.1
IRF8	NM_001363908.1 linkuse as main transcript	c.-93C>T		5_prime_UTR_variant	3/7		NP_001350837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF8	ENST00000268638.10 linkuse as main transcript	c.414C>T	p.Cys138=	synonymous_variant	4/9	1	NM_002163.4	ENSP00000268638	P1

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19992

AN:

152098

Hom.:

1377

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0915

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.123

GnomAD3 exomes

AF:

0.124

AC:

31230

AN:

251328

Hom.:

2130

AF XY:

0.124

AC XY:

16877

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.135

Gnomad AMR exome

AF:

0.118

Gnomad ASJ exome

AF:

0.129

Gnomad EAS exome

AF:

0.00163

Gnomad SAS exome

AF:

0.107

Gnomad FIN exome

AF:

0.180

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.133

AC:

194822

AN:

1461328

Hom.:

13815

Cov.:

AF XY:

0.133

AC XY:

96517

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.116

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.000983

Gnomad4 SAS exome

AF:

0.107

Gnomad4 FIN exome

AF:

0.182

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.130

GnomAD4 genome

AF:

0.131

AC:

20016

AN:

152216

Hom.:

1382

Cov.:

AF XY:

0.131

AC XY:

9714

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.133

Gnomad4 AMR

AF:

0.111

Gnomad4 ASJ

AF:

0.115

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0914

Gnomad4 FIN

AF:

0.176

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.125

Alfa

AF:

0.126

Hom.:

1482

Bravo

AF:

0.127

Asia WGS

AF:

0.0740

AC:

256

AN:

3478

EpiCase

AF:

0.130

EpiControl

AF:

0.125

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Immunodeficiency 32B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

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 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 18. Only high quality variants are reported. -

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

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.2

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