dbSNP rs368953537: IRF7:p.Asp290Val (chr11-613574-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001572.5(IRF7):c.869A>T(p.Asp290Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,418,470 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D290E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

IRF7
NM_001572.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.28

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF7	NM_001572.5 link	c.869A>T	p.Asp290Val	missense_variant	Exon 9 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.869A>T	p.Asp290Val	missense_variant	Exon 9 of 11	5	NM_001572.5	ENSP00000434009.2		Q92985-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.05e-7

AC:

AN:

1418470

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

702888

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32238

American (AMR)

AF:

0.00

AC:

AN:

38408

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23284

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38844

South Asian (SAS)

AF:

0.00

AC:

AN:

79722

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49888

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092302

Other (OTH)

AF:

0.00

AC:

AN:

58482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Uncertain

0.093

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

(source)

DANN

Benign

0.80

DEOGEN2

Uncertain

0.69

D;.;.;D;D;.

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.063

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.90

.;D;D;D;D;.

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.52

D;D;D;D;D;D

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.6

M;.;.;M;.;.

PhyloP100

1.3

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-5.8

D;D;D;.;.;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0020

D;D;D;.;.;D

Sift4G

Uncertain

0.0030

D;D;D;.;D;D

Polyphen

1.0

D;D;P;D;.;D

Vest4

0.34

MutPred

0.56

Gain of MoRF binding (P = 0.0343);.;.;Gain of MoRF binding (P = 0.0343);.;.;

MVP

0.84

MPC

0.61

ClinPred

0.99

GERP RS

2.8

Varity_R

0.67

gMVP

0.65

Mutation Taster

=76/24

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over