11-613966-C-T

Variant summary

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

The NM_001572.5(IRF7):​c.751G>A​(p.Ala251Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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. A251P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

IRF7
NM_001572.5 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.624
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]

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=0.06495896).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IRF7NM_001572.5 linkc.751G>A p.Ala251Thr missense_variant 7/11 ENST00000525445.6 NP_001563.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IRF7ENST00000525445.6 linkc.751G>A p.Ala251Thr missense_variant 7/115 NM_001572.5 ENSP00000434009.2 Q92985-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000435
AC:
1
AN:
229890
Hom.:
0
AF XY:
0.00000789
AC XY:
1
AN XY:
126744
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:
0.0000337
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1454304
Hom.:
0
Cov.:
34
AF XY:
0.00000276
AC XY:
2
AN XY:
723574
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:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
1.8
DANN
Benign
0.85
DEOGEN2
Benign
0.050
T;.;T;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.064
N
LIST_S2
Benign
0.37
.;T;T;.
M_CAP
Benign
0.076
D
MetaRNN
Benign
0.065
T;T;T;T
MetaSVM
Uncertain
-0.15
T
MutationAssessor
Benign
0.69
N;.;N;.
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.48
N;N;.;N
REVEL
Benign
0.23
Sift
Benign
0.66
T;T;.;T
Sift4G
Benign
0.41
T;T;.;T
Polyphen
0.0090
B;B;B;B
Vest4
0.10
MutPred
0.20
Gain of glycosylation at A251 (P = 7e-04);.;Gain of glycosylation at A251 (P = 7e-04);.;
MVP
0.57
MPC
0.10
ClinPred
0.061
T
GERP RS
-0.57
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.029
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs888494437; hg19: chr11-613966; API