11-613297-T-G

Variant summary

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

The NM_001572.5(IRF7):c.1146A>C(p.Gly382=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,607,992 control chromosomes in the GnomAD database, including 64,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G382G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.33 ( 9387 hom., cov: 31)

Exomes 𝑓: 0.27 ( 54971 hom. )

Consequence

IRF7
NM_001572.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -1.78

Variant links:

Genes affected

IRF7 (HGNC:6122): (interferon regulatory factor 7) This gene encodes interferon regulatory factor 7, a member of the interferon regulatory transcription factor (IRF) family. It has been shown to play a role in the transcriptional activation of virus-inducible cellular genes, including interferon beta chain genes. Inducible expression of IRF7 is largely restricted to lymphoid tissue. The encoded protein plays an important role in the innate immune response against DNA and RNA viruses. [provided by RefSeq, Jul 2021]

IRF7 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=-0.9).

BP6

Variant 11-613297-T-G is Benign according to our data. Variant chr11-613297-T-G is described in ClinVar as [Benign]. Clinvar id is 1170387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.78 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF7	NM_001572.5 linkuse as main transcript	c.1146A>C	p.Gly382=	synonymous_variant	9/11	ENST00000525445.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF7	ENST00000525445.6 linkuse as main transcript	c.1146A>C	p.Gly382=	synonymous_variant	9/11	5	NM_001572.5	P2	Q92985-1

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49340

AN:

151520

Hom.:

9371

Cov.:

show subpopulations

Gnomad AFR

AF:

0.519

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.0254

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.186

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.333

GnomAD3 exomes

AF:

0.252

AC:

60036

AN:

237930

Hom.:

8939

AF XY:

0.243

AC XY:

31792

AN XY:

130626

show subpopulations

Gnomad AFR exome

AF:

0.515

Gnomad AMR exome

AF:

0.325

Gnomad ASJ exome

AF:

0.333

Gnomad EAS exome

AF:

0.0284

Gnomad SAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.191

Gnomad NFE exome

AF:

0.267

Gnomad OTH exome

AF:

0.260

GnomAD4 exome

AF:

0.265

AC:

386252

AN:

1456358

Hom.:

54971

Cov.:

AF XY:

0.261

AC XY:

188798

AN XY:

724230

show subpopulations

Gnomad4 AFR exome

AF:

0.522

Gnomad4 AMR exome

AF:

0.323

Gnomad4 ASJ exome

AF:

0.335

Gnomad4 EAS exome

AF:

0.0229

Gnomad4 SAS exome

AF:

0.143

Gnomad4 FIN exome

AF:

0.198

Gnomad4 NFE exome

AF:

0.274

Gnomad4 OTH exome

AF:

0.273

GnomAD4 genome

AF:

0.326

AC:

49391

AN:

151634

Hom.:

9387

Cov.:

AF XY:

0.315

AC XY:

23339

AN XY:

74062

show subpopulations

Gnomad4 AFR

AF:

0.519

Gnomad4 AMR

AF:

0.307

Gnomad4 ASJ

AF:

0.348

Gnomad4 EAS

AF:

0.0255

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.186

Gnomad4 NFE

AF:

0.270

Gnomad4 OTH

AF:

0.331

Alfa

AF:

0.261

Hom.:

2304

Bravo

AF:

0.345

Asia WGS

AF:

0.126

AC:

438

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Immunodeficiency 39

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

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 59% of patients studied by a panel of primary immunodeficiencies. Number of patients: 56. Only high quality variants are reported. -

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

Cadd

Benign

5.1

Dann

Benign

0.76

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