19-33302101-TCGCCGCCGC-T
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3
The NM_004364.5(CEBPA):c.305_313delGCGGCGGCG(p.Gly102_Gly104del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000227 in 1,322,126 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. G102G) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000070 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000017 ( 0 hom. )
Consequence
CEBPA
NM_004364.5 disruptive_inframe_deletion
NM_004364.5 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.82
Publications
1 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]
CEBPA-DT (HGNC:25710): (CEBPA divergent transcript)
Genome browser will be placed here
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.305_313delGCGGCGGCG | p.Gly102_Gly104del | disruptive_inframe_deletion | Exon 1 of 1 | NP_004355.2 | |||
| CEBPA | c.410_418delGCGGCGGCG | p.Gly137_Gly139del | disruptive_inframe_deletion | Exon 1 of 1 | NP_001274353.1 | P49715-4 | |||
| CEBPA | c.263_271delGCGGCGGCG | p.Gly88_Gly90del | disruptive_inframe_deletion | 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.305_313delGCGGCGGCG | p.Gly102_Gly104del | disruptive_inframe_deletion | Exon 1 of 1 | ENSP00000427514.1 | P49715-1 | ||
| CEBPA-DT | n.46+313_46+321delGCCGCCGCC | intron | N/A | ||||||
| ENSG00000267727 | TSL:3 | n.*162_*170delCGCCGCCGC | downstream_gene | N/A |
Frequencies
GnomAD3 genomes 0.00000699 AC: 1AN: 142988Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
142988
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: 0.00000170 AC: 2AN: 1179138Hom.: 0 AF XY: 0.00000175 AC XY: 1AN XY: 572098 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1179138
Hom.:
AF XY:
AC XY:
1
AN XY:
572098
show subpopulations
African (AFR)
AF:
AC:
0
AN:
24108
American (AMR)
AF:
AC:
0
AN:
15604
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
18770
East Asian (EAS)
AF:
AC:
0
AN:
26088
South Asian (SAS)
AF:
AC:
0
AN:
42038
European-Finnish (FIN)
AF:
AC:
1
AN:
39430
Middle Eastern (MID)
AF:
AC:
0
AN:
3342
European-Non Finnish (NFE)
AF:
AC:
1
AN:
963130
Other (OTH)
AF:
AC:
0
AN:
46628
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000699 AC: 1AN: 142988Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 69714 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
142988
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
69714
show subpopulations
African (AFR)
AF:
AC:
0
AN:
39540
American (AMR)
AF:
AC:
0
AN:
14406
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3392
East Asian (EAS)
AF:
AC:
0
AN:
4048
South Asian (SAS)
AF:
AC:
0
AN:
3862
European-Finnish (FIN)
AF:
AC:
0
AN:
8908
Middle Eastern (MID)
AF:
AC:
0
AN:
308
European-Non Finnish (NFE)
AF:
AC:
1
AN:
65626
Other (OTH)
AF:
AC:
0
AN:
2026
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
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
Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
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>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
-
1
-
Acute myeloid leukemia (1)
-
1
-
Inborn genetic diseases (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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