rs760325316
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_001805.4(CEBPE):c.391C>T(p.Arg131Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,460,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
CEBPE
NM_001805.4 stop_gained
NM_001805.4 stop_gained
Scores
2
2
3
Clinical Significance
Conservation
PhyloP100: 1.23
Genes affected
CEBPE (HGNC:1836): (CCAAT enhancer binding protein epsilon) The protein encoded by this gene is a bZIP transcription factor which can bind as a homodimer to certain DNA regulatory regions. It can also form heterodimers with the related protein CEBP-delta. The encoded protein may be essential for terminal differentiation and functional maturation of committed granulocyte progenitor cells. Mutations in this gene have been associated with Specific Granule Deficiency, a rare congenital disorder. Multiple variants of this gene have been described, but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 7 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 14-23118701-G-A is Pathogenic according to our data. Variant chr14-23118701-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 530667.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEBPE | NM_001805.4 | c.391C>T | p.Arg131Ter | stop_gained | 1/2 | ENST00000206513.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEBPE | ENST00000206513.6 | c.391C>T | p.Arg131Ter | stop_gained | 1/2 | 1 | NM_001805.4 | P1 | |
CEBPE | ENST00000696121.1 | n.360C>T | non_coding_transcript_exon_variant | 2/3 | |||||
CEBPE | ENST00000696122.1 | n.137C>T | non_coding_transcript_exon_variant | 2/3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 247138Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134486
GnomAD3 exomes
AF:
AC:
3
AN:
247138
Hom.:
AF XY:
AC XY:
0
AN XY:
134486
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1460974Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 726868
GnomAD4 exome
AF:
AC:
12
AN:
1460974
Hom.:
Cov.:
32
AF XY:
AC XY:
5
AN XY:
726868
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
AF:
ExAC
?
AF:
AC:
1
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Specific granule deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2017 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CEBPE are known to be pathogenic (PMID: 11313242, 11435463). This variant has not been reported in the literature in individuals with CEBPE-related disease. This variant is present in population databases (rs760325316, ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg131*) in the CEBPE gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at