rs1131665

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.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. 18/23 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 the same amino acid substitution has been previously reported as Uncertain significance in 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:4O:1

Conservation

PhyloP100: -0.185

Publications

78 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=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 VariationId 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.

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.1235A>G	p.Gln412Arg	missense splice_region	Exon 9 of 11	NP_001563.2
IRF7	NM_004031.4		c.1274A>G	p.Gln425Arg	missense splice_region	Exon 8 of 10	NP_004022.2
IRF7	NM_001440440.1		c.1271A>G	p.Gln424Arg	missense splice_region	Exon 8 of 10	NP_001427369.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IRF7	ENST00000525445.6	TSL:5 MANE Select	c.1235A>G	p.Gln412Arg	missense splice_region	Exon 9 of 11	ENSP00000434009.2
IRF7	ENST00000397566.5	TSL:1	c.1274A>G	p.Gln425Arg	missense splice_region	Exon 7 of 9	ENSP00000380697.1
IRF7	ENST00000397570.5	TSL:1	c.1187A>G	p.Gln396Arg	missense splice_region	Exon 6 of 8	ENSP00000380700.2

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

GnomAD2 exomes

AF:

0.249

AC:

57004

AN:

228764

AF XY:

0.239

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 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

African (AFR)

AF:

0.522

AC:

16998

AN:

32556

American (AMR)

AF:

0.318

AC:

13067

AN:

41112

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

8246

AN:

24676

East Asian (EAS)

AF:

0.0228

AC:

899

AN:

39390

South Asian (SAS)

AF:

0.142

AC:

11966

AN:

84046

European-Finnish (FIN)

AF:

0.198

AC:

10148

AN:

51354

Middle Eastern (MID)

AF:

0.306

AC:

1729

AN:

5652

European-Non Finnish (NFE)

AF:

0.274

AC:

300508

AN:

1097126

Other (OTH)

AF:

0.272

AC:

16102

AN:

59140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

14484

28967

43451

57934

72418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10218

20436

30654

40872

51090

<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:

0.325

AC:

49421

AN:

152056

Hom.:

9390

Cov.:

AF XY:

0.314

AC XY:

23361

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.518

AC:

21497

AN:

41464

American (AMR)

AF:

0.307

AC:

4692

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1203

AN:

3470

East Asian (EAS)

AF:

0.0256

AC:

132

AN:

5160

South Asian (SAS)

AF:

0.128

AC:

616

AN:

4824

European-Finnish (FIN)

AF:

0.185

AC:

1959

AN:

10606

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.270

AC:

18334

AN:

67930

Other (OTH)

AF:

0.330

AC:

698

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1609

3218

4827

6436

8045

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.285

Hom.:

18335

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency 39 (2)

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.066

(source)

DANN

Benign

0.40

DEOGEN2

Benign

0.33

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.27

MetaRNN

Benign

0.00011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.17

PhyloP100

-0.18

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.13

REVEL

Benign

0.28

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.045

MPC

0.11

ClinPred

0.0017

GERP RS

-5.9

Varity_R

0.060

gMVP

0.31

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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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