chr4-184408164-T-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002199.4(IRF2):c.523A>T(p.Ile175Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000707 in 1,579,188 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00038 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00074 ( 1 hom. )
Consequence
IRF2
NM_002199.4 missense
NM_002199.4 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 3.75
Genes affected
IRF2 (HGNC:6117): (interferon regulatory factor 2) IRF2 encodes interferon regulatory factor 2, a member of the interferon regulatory transcription factor (IRF) family. IRF2 competitively inhibits the IRF1-mediated transcriptional activation of interferons alpha and beta, and presumably other genes that employ IRF1 for transcription activation. However, IRF2 also functions as a transcriptional activator of histone H4. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.06925094).
BS2
High AC in GnomAd4 at 58 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IRF2 | NM_002199.4 | c.523A>T | p.Ile175Phe | missense_variant | 6/9 | ENST00000393593.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IRF2 | ENST00000393593.8 | c.523A>T | p.Ile175Phe | missense_variant | 6/9 | 1 | NM_002199.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000381 AC: 58AN: 152194Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000283 AC: 71AN: 250498Hom.: 0 AF XY: 0.000296 AC XY: 40AN XY: 135318
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GnomAD4 exome AF: 0.000742 AC: 1059AN: 1426876Hom.: 1 Cov.: 25 AF XY: 0.000708 AC XY: 504AN XY: 712216
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GnomAD4 genome AF: 0.000381 AC: 58AN: 152312Hom.: 1 Cov.: 32 AF XY: 0.000295 AC XY: 22AN XY: 74476
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 30, 2022 | The c.523A>T (p.I175F) alteration is located in exon 6 (coding exon 5) of the IRF2 gene. This alteration results from a A to T substitution at nucleotide position 523, causing the isoleucine (I) at amino acid position 175 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;.
Polyphen
B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at