rs1061502

Positions:

chr11-614318-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.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. 15/20 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 0.33 ( 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

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=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/exons	MANE	Protein	UniProt
IRF7	NM_001572.5 linkuse as main transcript	c.535A>G	p.Lys179Glu	missense_variant	6/11	ENST00000525445.6	NP_001563.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF7	ENST00000525445.6 linkuse as main transcript	c.535A>G	p.Lys179Glu	missense_variant	6/11	5	NM_001572.5	ENSP00000434009	P2	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

GnomAD3 exomes

AF:

0.253

AC:

61686

AN:

243768

Hom.:

9205

AF XY:

0.242

AC XY:

32092

AN XY:

132454

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 SAS exome

AF:

0.140

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

Gnomad4 AFR exome

AF:

0.523

Gnomad4 AMR exome

AF:

0.321

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:

0.325

AC:

49460

AN:

152078

Hom.:

9408

Cov.:

AF XY:

0.315

AC XY:

23381

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.519

Gnomad4 AMR

AF:

0.307

Gnomad4 ASJ

AF:

0.347

Gnomad4 EAS

AF:

0.0258

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.185

Gnomad4 NFE

AF:

0.270

Gnomad4 OTH

AF:

0.331

Alfa

AF:

0.275

Hom.:

4347

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not provided

Benign:1Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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. -

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. -

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

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;.;.

MutationTaster

Benign

1.0

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

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

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