Genetic Variant IRF7:p.Ala503Thr (chr11-612650-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001572.5(IRF7):c.1507G>A(p.Ala503Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,612,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. A503V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

IRF7
NM_001572.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.296

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07552722).

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	UniProt
IRF7	NM_001572.5	MANE Select	c.1507G>A	p.Ala503Thr	missense	Exon 11 of 11	NP_001563.2
IRF7	NM_004031.4		c.1546G>A	p.Ala516Thr	missense	Exon 10 of 10	NP_004022.2	Q92985-4
IRF7	NM_001440440.1		c.1543G>A	p.Ala515Thr	missense	Exon 10 of 10	NP_001427369.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IRF7	ENST00000525445.6	TSL:5 MANE Select	c.1507G>A	p.Ala503Thr	missense	Exon 11 of 11	ENSP00000434009.2	Q92985-1
IRF7	ENST00000397566.5	TSL:1	c.1546G>A	p.Ala516Thr	missense	Exon 9 of 9	ENSP00000380697.1	Q92985-4
IRF7	ENST00000397570.5	TSL:1	c.1459G>A	p.Ala487Thr	missense	Exon 8 of 8	ENSP00000380700.2	M9RSF4

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000359

AC:

AN:

250408

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1460376

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726540

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.0000894

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52034

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111930

Other (OTH)

AF:

0.0000331

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41534

American (AMR)

AF:

0.000131

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000657

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.080

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.63

M_CAP

Benign

0.065

MetaRNN

Benign

0.076

MetaSVM

Uncertain

0.29

MutationAssessor

Benign

1.6

PhyloP100

-0.30

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.1

REVEL

Benign

0.27

Sift

Uncertain

0.027

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.17

MVP

0.84

MPC

0.51

ClinPred

0.087

GERP RS

1.8

Varity_R

0.15

gMVP

0.28

Mutation Taster

=89/11

polymorphism

(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

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

Computational scores

Splicing

Publications

Other links and lift over