rs201036875

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001572.5(IRF7):c.392G>A(p.Arg131Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000489 in 1,544,066 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 18/24 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R131G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00049 ( 5 hom. )

Consequence

IRF7
NM_001572.5 missense, splice_region

Scores

Splicing: ADA: 0.00006317

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:5B:3

Conservation

PhyloP100: -0.470

Publications

6 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007612765).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001572.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IRF7	NM_001572.5	MANE Select	c.392G>A	p.Arg131Gln	missense splice_region	Exon 4 of 11	NP_001563.2
IRF7	NM_004031.4		c.431G>A	p.Arg144Gln	missense splice_region	Exon 3 of 10	NP_004022.2
IRF7	NM_001440440.1		c.431G>A	p.Arg144Gln	missense splice_region	Exon 3 of 10	NP_001427369.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IRF7	ENST00000525445.6	TSL:5 MANE Select	c.392G>A	p.Arg131Gln	missense splice_region	Exon 4 of 11	ENSP00000434009.2
IRF7	ENST00000397566.5	TSL:1	c.431G>A	p.Arg144Gln	missense splice_region	Exon 2 of 9	ENSP00000380697.1
IRF7	ENST00000397570.5	TSL:1	c.431G>A	p.Arg144Gln	missense splice_region	Exon 2 of 8	ENSP00000380700.2

Frequencies

GnomAD3 genomes

AF:

0.000479

AC:

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000655

AC:

AN:

138912

AF XY:

0.000545

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000859

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000709

Gnomad OTH exome

AF:

0.00271

GnomAD4 exome

AF:

0.000491

AC:

683

AN:

1391680

Hom.:

Cov.:

AF XY:

0.000516

AC XY:

354

AN XY:

686682

show subpopulations

African (AFR)

AF:

0.000255

AC:

AN:

31382

American (AMR)

AF:

0.00125

AC:

AN:

34406

Ashkenazi Jewish (ASJ)

AF:

0.00104

AC:

AN:

24990

East Asian (EAS)

AF:

0.00

AC:

AN:

35692

South Asian (SAS)

AF:

0.000571

AC:

AN:

78852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45356

Middle Eastern (MID)

AF:

0.0158

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

0.000362

AC:

390

AN:

1077546

Other (OTH)

AF:

0.00140

AC:

AN:

57776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

125

166

208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000472

AC:

AN:

152386

Hom.:

Cov.:

AF XY:

0.000496

AC XY:

AN XY:

74524

show subpopulations

African (AFR)

AF:

0.0000721

AC:

AN:

41594

American (AMR)

AF:

0.00131

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00103

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000470

AC:

AN:

68036

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000970

Hom.:

Bravo

AF:

0.000518

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000620

AC:

ExAC

AF:

0.000276

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency 39 (3)

not provided (3)

IRF7-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.042

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.78

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.0064

MetaSVM

Uncertain

-0.047

MutationAssessor

Benign

1.8

PhyloP100

-0.47

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.41

REVEL

Benign

0.22

Sift

Benign

0.65

Sift4G

Benign

0.62

Polyphen

0.79

Vest4

0.17

MVP

0.78

MPC

0.29

ClinPred

0.064

GERP RS

-0.98

Varity_R

0.025

gMVP

0.22

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000063

dbscSNV1_RF

Benign

0.0020

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over