GeneBe

rs1555377483

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_024496.4(IRF2BPL):​c.376C>T​(p.Gln126*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 29)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

IRF2BPL
NM_024496.4 stop_gained

Scores

2
2
2

Clinical Significance

Pathogenic no assertion criteria provided P:3

Conservation

PhyloP100: 3.15

Publications

1 publications found
Variant links:
Genes affected
IRF2BPL (HGNC:14282): (interferon regulatory factor 2 binding protein like) This gene encodes a transcription factor that may play a role in regulating female reproductive function. [provided by RefSeq, Jun 2012]
LINC02289 (HGNC:53205): (long intergenic non-protein coding RNA 2289)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 11 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 68 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-77027417-G-A is Pathogenic according to our data. Variant chr14-77027417-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 559610.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024496.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
IRF2BPL
NM_024496.4
MANE Select
c.376C>Tp.Gln126*
stop_gained
Exon 1 of 1NP_078772.1Q9H1B7
LOC107984638
NR_190000.1
n.-51G>A
upstream_gene
N/A
LOC107984638
NR_190001.1
n.-51G>A
upstream_gene
N/A

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
IRF2BPL
ENST00000238647.5
TSL:6 MANE Select
c.376C>Tp.Gln126*
stop_gained
Exon 1 of 1ENSP00000238647.3Q9H1B7
LINC02289
ENST00000716908.1
n.304+13637C>T
intron
N/A

Frequencies

GnomAD3 genomes
Cov.:
29
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1323954
Hom.:
0
Cov.:
65
AF XY:
0.00
AC XY:
0
AN XY:
653072
African (AFR)
AF:
0.00
AC:
0
AN:
26552
American (AMR)
AF:
0.00
AC:
0
AN:
27452
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22962
East Asian (EAS)
AF:
0.00
AC:
0
AN:
28856
South Asian (SAS)
AF:
0.00
AC:
0
AN:
72604
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
44676
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4030
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1042558
Other (OTH)
AF:
0.00
AC:
0
AN:
54264
GnomAD4 genome
Cov.:
29

ClinVar

ClinVar submissions
Significance:Pathogenic
Revision:no assertion criteria provided
View on ClinVar
Pathogenic
VUS
Benign
Condition
2
-
-
not provided (2)
1
-
-
Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.45
D
BayesDel_noAF
Pathogenic
0.41
CADD
Pathogenic
36
DANN
Uncertain
1.0
Eigen
Uncertain
0.29
Eigen_PC
Benign
0.0049
FATHMM_MKL
Benign
0.57
D
PhyloP100
3.1
Vest4
0.078
GERP RS
2.2
Mutation Taster
=0/200
disease causing (ClinVar)

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: rs1555377483; hg19: chr14-77493760; API