11-612650-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.296
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07552722).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IRF7NM_001572.5 linkc.1507G>A p.Ala503Thr missense_variant Exon 11 of 11 ENST00000525445.6 NP_001563.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IRF7ENST00000525445.6 linkc.1507G>A p.Ala503Thr missense_variant Exon 11 of 11 5 NM_001572.5 ENSP00000434009.2 Q92985-1

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152116
Hom.:
0
Cov.:
33
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
GnomAD3 exomes
AF:
0.0000359
AC:
9
AN:
250408
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135560
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000753
AC:
11
AN:
1460376
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
726540
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152234
Hom.:
0
Cov.:
33
AF XY:
0.000107
AC XY:
8
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000967
Hom.:
0
Bravo
AF:
0.0000718
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 26, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1546G>A (p.A516T) alteration is located in exon 9 (coding exon 9) of the IRF7 gene. This alteration results from a G to A substitution at nucleotide position 1546, causing the alanine (A) at amino acid position 516 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.080
T;.;.;T;T;.
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.76
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.63
.;T;T;T;T;.
M_CAP
Benign
0.065
D
MetaRNN
Benign
0.076
T;T;T;T;T;T
MetaSVM
Uncertain
0.29
D
MutationAssessor
Benign
1.6
L;.;.;L;.;.
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.1
N;N;N;.;.;N
REVEL
Benign
0.27
Sift
Uncertain
0.027
D;D;D;.;.;D
Sift4G
Pathogenic
0.0
D;D;D;.;D;D
Polyphen
0.98
D;B;D;D;.;B
Vest4
0.17
MVP
0.84
MPC
0.51
ClinPred
0.087
T
GERP RS
1.8
Varity_R
0.15
gMVP
0.28

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.

Other links and lift over

dbSNP: rs140470055; hg19: chr11-612650; API