1-234609296-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182972.3(IRF2BP2):​c.199C>A​(p.Pro67Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. P67S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

IRF2BP2
NM_182972.3 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.95

Publications

0 publications found
Variant links:
Genes affected
IRF2BP2 (HGNC:21729): (interferon regulatory factor 2 binding protein 2) This gene encodes an interferon regulatory factor-2 (IRF2) binding protein that interacts with the C-terminal transcriptional repression domain of IRF2. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]
LINC00184 (HGNC:37192): (long intergenic non-protein coding RNA 184)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12803471).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IRF2BP2NM_182972.3 linkc.199C>A p.Pro67Thr missense_variant Exon 1 of 2 ENST00000366609.4 NP_892017.2 Q7Z5L9-1
IRF2BP2NM_001077397.1 linkc.199C>A p.Pro67Thr missense_variant Exon 1 of 2 NP_001070865.1 Q7Z5L9-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IRF2BP2ENST00000366609.4 linkc.199C>A p.Pro67Thr missense_variant Exon 1 of 2 1 NM_182972.3 ENSP00000355568.3 Q7Z5L9-1
IRF2BP2ENST00000366610.8 linkc.199C>A p.Pro67Thr missense_variant Exon 1 of 2 1 ENSP00000355569.3 Q7Z5L9-2
LINC00184ENST00000796406.1 linkn.2G>T non_coding_transcript_exon_variant Exon 1 of 4
ENSG00000228830ENST00000436039.1 linkn.631-125G>T intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1327104
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
654460
African (AFR)
AF:
0.00
AC:
0
AN:
26864
American (AMR)
AF:
0.00
AC:
0
AN:
27176
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22946
East Asian (EAS)
AF:
0.00
AC:
0
AN:
28570
South Asian (SAS)
AF:
0.00
AC:
0
AN:
72584
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
45448
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4086
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1044992
Other (OTH)
AF:
0.00
AC:
0
AN:
54438
GnomAD4 genome
Cov.:
30
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
18
DANN
Benign
0.91
DEOGEN2
Benign
0.016
.;T
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.79
T;T
M_CAP
Benign
0.055
D
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N;N
PhyloP100
3.9
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.066
Sift
Benign
0.032
D;T
Sift4G
Benign
0.084
T;T
Polyphen
0.56
P;B
Vest4
0.15
MutPred
0.17
Gain of phosphorylation at P67 (P = 0.0392);Gain of phosphorylation at P67 (P = 0.0392);
MVP
0.28
MPC
1.3
ClinPred
0.40
T
GERP RS
2.7
PromoterAI
-0.066
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.3
Varity_R
0.081
gMVP
0.20
Mutation Taster
=71/29
polymorphism

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

Other links and lift over

dbSNP: rs944069598; hg19: chr1-234745042; API