rs1131665

Positions:

chr11-613208-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001572.5(IRF7):c.1235A>G(p.Gln412Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,587,108 control chromosomes in the GnomAD database, including 63,213 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.

Frequency

Genomes: 𝑓 0.33 ( 9390 hom., cov: 32)

Exomes 𝑓: 0.26 ( 53823 hom. )

Consequence

IRF7
NM_001572.5 missense, splice_region

Scores

Splicing: ADA: 0.0002884

Clinical Significance

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

Conservation

PhyloP100: -0.185

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0981237E-4).

BP6

Variant 11-613208-T-C is Benign according to our data. Variant chr11-613208-T-C is described in ClinVar as [Benign]. Clinvar id is 1170386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.1235A>G	p.Gln412Arg	missense_variant, splice_region_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.1235A>G	p.Gln412Arg	missense_variant, splice_region_variant	9/11	5	NM_001572.5	P2	Q92985-1

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

49370

AN:

151938

Hom.:

9374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.519

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.0255

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.332

GnomAD3 exomes

AF:

0.249

AC:

57004

AN:

228764

Hom.:

8330

AF XY:

0.239

AC XY:

29916

AN XY:

124934

show subpopulations

Gnomad AFR exome

AF:

0.513

Gnomad AMR exome

AF:

0.320

Gnomad ASJ exome

AF:

0.335

Gnomad EAS exome

AF:

0.0280

Gnomad SAS exome

AF:

0.139

Gnomad FIN exome

AF:

0.186

Gnomad NFE exome

AF:

0.263

Gnomad OTH exome

AF:

0.259

GnomAD4 exome

AF:

0.265

AC:

379663

AN:

1435052

Hom.:

53823

Cov.:

AF XY:

0.260

AC XY:

184903

AN XY:

711396

show subpopulations

Gnomad4 AFR exome

AF:

0.522

Gnomad4 AMR exome

AF:

0.318

Gnomad4 ASJ exome

AF:

0.334

Gnomad4 EAS exome

AF:

0.0228

Gnomad4 SAS exome

AF:

0.142

Gnomad4 FIN exome

AF:

0.198

Gnomad4 NFE exome

AF:

0.274

Gnomad4 OTH exome

AF:

0.272

GnomAD4 genome

AF:

0.325

AC:

49421

AN:

152056

Hom.:

9390

Cov.:

AF XY:

0.314

AC XY:

23361

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.518

Gnomad4 AMR

AF:

0.307

Gnomad4 ASJ

AF:

0.347

Gnomad4 EAS

AF:

0.0256

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.185

Gnomad4 NFE

AF:

0.270

Gnomad4 OTH

AF:

0.330

Alfa

AF:

0.279

Hom.:

6451

Bravo

AF:

0.345

TwinsUK

AF:

0.261

AC:

968

ALSPAC

AF:

0.274

AC:

1057

ESP6500AA

AF:

0.509

AC:

2234

ESP6500EA

AF:

0.286

AC:

2458

ExAC

AF:

0.248

AC:

30055

Asia WGS

AF:

0.126

AC:

439

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

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.066

DANN

Benign

0.40

DEOGEN2

Benign

0.33

T;.;.;T;T;.

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.27

.;T;T;T;T;.

MetaRNN

Benign

0.00011

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.17

N;.;.;N;.;.

MutationTaster

Benign

1.0

P;P;P;P;P;P;P

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.13

N;N;N;.;.;N

REVEL

Benign

0.28

Sift

Benign

1.0

T;T;T;.;.;T

Sift4G

Benign

1.0

T;T;T;.;T;T

Polyphen

0.0

B;B;B;B;.;B

Vest4

0.045

MPC

0.11

ClinPred

0.0017

GERP RS

-5.9

Varity_R

0.060

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00029

dbscSNV1_RF

Benign

0.020

SpliceAI score (max)

0.050

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