NM_004364.5:c.558_566dupGCCGCCGCC
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3
The NM_004364.5(CEBPA):c.558_566dupGCCGCCGCC(p.Pro187_Pro189dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000229 in 1,310,768 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P189P) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000068 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000017 ( 0 hom. )
Consequence
CEBPA
NM_004364.5 disruptive_inframe_insertion
NM_004364.5 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.21
Publications
2 publications found
Genes affected
CEBPA (HGNC:1833): (CCAAT enhancer binding protein alpha) This intronless gene encodes a transcription factor that contains a basic leucine zipper (bZIP) domain and recognizes the CCAAT motif in the promoters of target genes. The encoded protein functions in homodimers and also heterodimers with CCAAT/enhancer-binding proteins beta and gamma. Activity of this protein can modulate the expression of genes involved in cell cycle regulation as well as in body weight homeostasis. Mutation of this gene is associated with acute myeloid leukemia. The use of alternative in-frame non-AUG (GUG) and AUG start codons results in protein isoforms with different lengths. Differential translation initiation is mediated by an out-of-frame, upstream open reading frame which is located between the GUG and the first AUG start codons. [provided by RefSeq, Dec 2013]
ENSG00000267727 (HGNC:):
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_004364.5
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_004364.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CEBPA | MANE Select | c.558_566dupGCCGCCGCC | p.Pro187_Pro189dup | disruptive_inframe_insertion | Exon 1 of 1 | NP_004355.2 | |||
| CEBPA | c.663_671dupGCCGCCGCC | p.Pro222_Pro224dup | disruptive_inframe_insertion | Exon 1 of 1 | NP_001274353.1 | P49715-4 | |||
| CEBPA | c.516_524dupGCCGCCGCC | p.Pro173_Pro175dup | disruptive_inframe_insertion | Exon 1 of 1 | NP_001274364.1 | P49715-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CEBPA | TSL:6 MANE Select | c.558_566dupGCCGCCGCC | p.Pro187_Pro189dup | disruptive_inframe_insertion | Exon 1 of 1 | ENSP00000427514.1 | P49715-1 | ||
| ENSG00000267727 | TSL:3 | n.403_411dupGGCGGCGGC | non_coding_transcript_exon | Exon 2 of 2 | |||||
| CEBPA-DT | n.46+62_46+70dupGGCGGCGGC | intron | N/A |
Frequencies
GnomAD3 genomes 0.00000675 AC: 1AN: 148062Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
148062
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000172 AC: 2AN: 1162706Hom.: 0 Cov.: 32 AF XY: 0.00000176 AC XY: 1AN XY: 568590 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1162706
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
568590
show subpopulations
African (AFR)
AF:
AC:
0
AN:
23048
American (AMR)
AF:
AC:
0
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
16996
East Asian (EAS)
AF:
AC:
0
AN:
23998
South Asian (SAS)
AF:
AC:
1
AN:
48148
European-Finnish (FIN)
AF:
AC:
0
AN:
26508
Middle Eastern (MID)
AF:
AC:
1
AN:
3124
European-Non Finnish (NFE)
AF:
AC:
0
AN:
959906
Other (OTH)
AF:
AC:
0
AN:
45694
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
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>80
Age
GnomAD4 genome 0.00000675 AC: 1AN: 148062Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 72100 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
148062
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
72100
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
40992
American (AMR)
AF:
AC:
0
AN:
14940
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3398
East Asian (EAS)
AF:
AC:
0
AN:
5092
South Asian (SAS)
AF:
AC:
0
AN:
4810
European-Finnish (FIN)
AF:
AC:
0
AN:
9160
Middle Eastern (MID)
AF:
AC:
0
AN:
312
European-Non Finnish (NFE)
AF:
AC:
0
AN:
66410
Other (OTH)
AF:
AC:
0
AN:
2040
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Acute myeloid leukemia (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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