Genetic Variant NM_001572.5:c.317T>G (chr11-614874-A-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001572.5(IRF7):c.317T>G(p.Val106Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,426,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. V106M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

IRF7
NM_001572.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.205

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38201386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF7	NM_001572.5 link	c.317T>G	p.Val106Gly	missense_variant	Exon 4 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.317T>G	p.Val106Gly	missense_variant	Exon 4 of 11	5	NM_001572.5	ENSP00000434009.2		Q92985-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1426270

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

706910

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32510

American (AMR)

AF:

0.00

AC:

AN:

40516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25484

East Asian (EAS)

AF:

0.00

AC:

AN:

37388

South Asian (SAS)

AF:

0.00

AC:

AN:

81750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47738

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1096142

Other (OTH)

AF:

0.00

AC:

AN:

59004

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

0.30

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

(source)

DANN

Benign

0.64

DEOGEN2

Uncertain

0.72

D;.;.;D;D;.;.;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.67

.;T;T;T;T;.;T;T

M_CAP

Pathogenic

0.29

MetaRNN

Benign

0.38

T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.57

MutationAssessor

Uncertain

2.5

M;.;M;M;.;.;.;.

PhyloP100

-0.20

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.5

D;D;D;.;.;D;.;.

REVEL

Uncertain

0.47

Sift

Uncertain

0.0090

D;D;D;.;.;D;.;.

Sift4G

Benign

0.41

T;T;T;.;T;T;.;.

Polyphen

1.0

D;D;D;D;.;D;.;.

Vest4

0.29

MutPred

0.44

Gain of disorder (P = 0.0195);.;Gain of disorder (P = 0.0195);Gain of disorder (P = 0.0195);.;.;Gain of disorder (P = 0.0195);.;

MVP

0.64

MPC

0.50

ClinPred

0.31

GERP RS

0.45

Varity_R

0.33

gMVP

0.53

Mutation Taster

=71/29

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