rs1061502

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001572.5(IRF7):c.535A>G(p.Lys179Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,610,258 control chromosomes in the GnomAD database, including 64,369 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. K179K) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.33 ( 9408 hom., cov: 33)

Exomes 𝑓: 0.27 ( 54961 hom. )

Consequence

IRF7
NM_001572.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -3.69

Publications

57 publications found

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 Gene-Disease associations (from GenCC):

immunodeficiency 39
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

IRF7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.8386428E-5).

BP6

Variant 11-614318-T-C is Benign according to our data. Variant chr11-614318-T-C is described in ClinVar as [Benign]. Clinvar id is 1170388.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 rank	MANE	Protein	UniProt
IRF7	NM_001572.5 link	c.535A>G	p.Lys179Glu	missense_variant	Exon 6 of 11	ENST00000525445.6	NP_001563.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF7	ENST00000525445.6 link	c.535A>G	p.Lys179Glu	missense_variant	Exon 6 of 11	5	NM_001572.5	ENSP00000434009.2		Q92985-1

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

49409

AN:

151960

Hom.:

9392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.519

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.0257

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.338

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.333

GnomAD2 exomes

AF:

0.253

AC:

61686

AN:

243768

AF XY:

0.242

show subpopulations

Gnomad AFR exome

AF:

0.524

Gnomad AMR exome

AF:

0.323

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.0280

Gnomad FIN exome

AF:

0.188

Gnomad NFE exome

AF:

0.266

Gnomad OTH exome

AF:

0.259

GnomAD4 exome

AF:

0.265

AC:

386586

AN:

1458180

Hom.:

54961

Cov.:

AF XY:

0.261

AC XY:

188953

AN XY:

725208

show subpopulations

African (AFR)

AF:

0.523

AC:

17505

AN:

33448

American (AMR)

AF:

0.321

AC:

14206

AN:

44298

Ashkenazi Jewish (ASJ)

AF:

0.335

AC:

8726

AN:

26084

East Asian (EAS)

AF:

0.0229

AC:

907

AN:

39672

South Asian (SAS)

AF:

0.143

AC:

12255

AN:

85946

European-Finnish (FIN)

AF:

0.198

AC:

10283

AN:

51842

Middle Eastern (MID)

AF:

0.305

AC:

1754

AN:

5760

European-Non Finnish (NFE)

AF:

0.274

AC:

304504

AN:

1110828

Other (OTH)

AF:

0.273

AC:

16446

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

16204

32408

48611

64815

81019

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.325

AC:

49460

AN:

152078

Hom.:

9408

Cov.:

AF XY:

0.315

AC XY:

23381

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.519

AC:

21536

AN:

41472

American (AMR)

AF:

0.307

AC:

4686

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1204

AN:

3472

East Asian (EAS)

AF:

0.0258

AC:

133

AN:

5162

South Asian (SAS)

AF:

0.127

AC:

614

AN:

4828

European-Finnish (FIN)

AF:

0.185

AC:

1965

AN:

10600

Middle Eastern (MID)

AF:

0.346

AC:

101

AN:

292

European-Non Finnish (NFE)

AF:

0.270

AC:

18334

AN:

67950

Other (OTH)

AF:

0.331

AC:

698

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1654

3309

4963

6618

8272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.281

Hom.:

4813

Bravo

AF:

0.346

TwinsUK

AF:

0.268

AC:

995

ALSPAC

AF:

0.278

AC:

1073

ESP6500AA

AF:

0.524

AC:

2304

ESP6500EA

AF:

0.292

AC:

2507

ExAC

AF:

0.252

AC:

30382

Asia WGS

AF:

0.126

AC:

439

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Immunodeficiency 39

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

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. -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.0030

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.036

T;.;.;T;T;.

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.70

.;T;T;T;T;.

MetaRNN

Benign

0.000038

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.76

N;.;N;N;.;.

PhyloP100

-3.7

PrimateAI

Benign

0.46

PROVEAN

Benign

0.48

N;N;N;.;.;N

REVEL

Benign

0.26

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

0.048

MPC

0.15

ClinPred

0.0010

GERP RS

-5.2

Varity_R

0.038

gMVP

0.32

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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rs1061502

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over