rs763456786

Positions:

chr11-613583-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001572.5(IRF7):c.860G>C(p.Gly287Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000474 in 1,562,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

IRF7
NM_001572.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0730

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0662542).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF7	NM_001572.5 linkuse as main transcript	c.860G>C	p.Gly287Ala	missense_variant	9/11	ENST00000525445.6	NP_001563.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF7	ENST00000525445.6 linkuse as main transcript	c.860G>C	p.Gly287Ala	missense_variant	9/11	5	NM_001572.5	ENSP00000434009	P2	Q92985-1

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

150704

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000591

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

193418

Hom.:

AF XY:

0.0000378

AC XY:

AN XY:

105916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000103

Gnomad OTH exome

AF:

0.000215

GnomAD4 exome

AF:

0.0000496

AC:

AN:

1412120

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

699228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000202

Gnomad4 NFE exome

AF:

0.0000624

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000265

AC:

AN:

150704

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73508

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000591

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000144

Hom.:

ExAC

AF:

0.0000670

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Immunodeficiency 39

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 27, 2023

This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 300 of the IRF7 protein (p.Gly300Ala). This variant is present in population databases (rs763456786, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with IRF7-related conditions. ClinVar contains an entry for this variant (Variation ID: 542688). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt IRF7 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.56

CADD

Benign

4.8

DANN

Benign

0.81

DEOGEN2

Benign

0.075

T;.;.;T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.75

.;T;T;T;T;.

M_CAP

Benign

0.023

MetaRNN

Benign

0.066

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.;.;M;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.8

N;N;N;.;.;N

REVEL

Benign

0.025

Sift

Benign

0.37

T;T;T;.;.;T

Sift4G

Benign

0.70

T;T;T;.;T;T

Polyphen

0.26

B;B;B;B;.;B

Vest4

0.15

MVP

0.45

MPC

0.13

ClinPred

0.065

GERP RS

2.1

Varity_R

0.057

gMVP

0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over