Variant chr19-49659652-C-G 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_001571.6(IRF3):c.1280G>C(p.Ser427Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,611,434 control chromosomes in the GnomAD database, including 106,655 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.43 ( 16020 hom., cov: 31)

Exomes 𝑓: 0.34 ( 90635 hom. )

Consequence

IRF3
NM_001571.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.636

Variant links:

Genes affected

IRF3 (HGNC:6118): (interferon regulatory factor 3) This gene encodes a member of the interferon regulatory transcription factor (IRF) family. The encoded protein is found in an inactive cytoplasmic form that upon serine/threonine phosphorylation forms a complex with CREBBP. This complex translocates to the nucleus and activates the transcription of interferons alpha and beta, as well as other interferon-induced genes. The protein plays an important role in the innate immune response against DNA and RNA viruses. Mutations in this gene are associated with Encephalopathy, acute, infection-induced, herpes-specific, 7. [provided by RefSeq, Sep 2020]

IRF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.883909E-6).

BP6

Variant 19-49659652-C-G is Benign according to our data. Variant chr19-49659652-C-G is described in ClinVar as [Benign]. Clinvar id is 2688047.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF3	NM_001571.6 linkuse as main transcript	c.1280G>C	p.Ser427Thr	missense_variant	8/8	ENST00000377139.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF3	ENST00000377139.8 linkuse as main transcript	c.1280G>C	p.Ser427Thr	missense_variant	8/8	1	NM_001571.6	P1	Q14653-1

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65728

AN:

151832

Hom.:

15970

Cov.:

show subpopulations

Gnomad AFR

AF:

0.660

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.355

Gnomad SAS

AF:

0.496

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.420

GnomAD3 exomes

AF:

0.387

AC:

95034

AN:

245682

Hom.:

19613

AF XY:

0.382

AC XY:

50753

AN XY:

132968

show subpopulations

Gnomad AFR exome

AF:

0.668

Gnomad AMR exome

AF:

0.473

Gnomad ASJ exome

AF:

0.357

Gnomad EAS exome

AF:

0.351

Gnomad SAS exome

AF:

0.475

Gnomad FIN exome

AF:

0.264

Gnomad NFE exome

AF:

0.328

Gnomad OTH exome

AF:

0.370

GnomAD4 exome

AF:

0.344

AC:

502778

AN:

1459486

Hom.:

90635

Cov.:

AF XY:

0.347

AC XY:

252061

AN XY:

725904

show subpopulations

Gnomad4 AFR exome

AF:

0.669

Gnomad4 AMR exome

AF:

0.467

Gnomad4 ASJ exome

AF:

0.355

Gnomad4 EAS exome

AF:

0.365

Gnomad4 SAS exome

AF:

0.469

Gnomad4 FIN exome

AF:

0.261

Gnomad4 NFE exome

AF:

0.321

Gnomad4 OTH exome

AF:

0.371

GnomAD4 genome

AF:

0.433

AC:

65829

AN:

151948

Hom.:

16020

Cov.:

AF XY:

0.429

AC XY:

31853

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.661

Gnomad4 AMR

AF:

0.439

Gnomad4 ASJ

AF:

0.353

Gnomad4 EAS

AF:

0.354

Gnomad4 SAS

AF:

0.494

Gnomad4 FIN

AF:

0.253

Gnomad4 NFE

AF:

0.328

Gnomad4 OTH

AF:

0.425

Alfa

AF:

0.357

Hom.:

3182

Bravo

AF:

0.456

TwinsUK

AF:

0.324

AC:

1203

ALSPAC

AF:

0.314

AC:

1211

ESP6500AA

AF:

0.663

AC:

2920

ESP6500EA

AF:

0.316

AC:

2715

ExAC

AF:

0.390

AC:

47254

Asia WGS

AF:

0.507

AC:

1759

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 63% of patients studied by a panel of primary immunodeficiencies. Number of patients: 60. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Uncertain

0.010

CADD

Benign

0.24

DANN

Benign

0.35

DEOGEN2

Benign

0.012

.;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.19

T;T;T

MetaRNN

Benign

0.0000029

T;T;T

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.26

Vest4

0.041

MPC

0.48

ClinPred

0.00066

GERP RS

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.060

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