rs1555741948
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM4PP5
The NM_004364.5(CEBPA):c.991_992insAGAAGGTGCTGGAGCTGACCAGTGACAATGACCGCCTGCGCAAGCGGGTGGAACAGC(p.Gln312_Gln330dup) variant causes a inframe insertion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
CEBPA
NM_004364.5 inframe_insertion
NM_004364.5 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.92
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM1
?
In a domain bZIP (size 63) in uniprot entity CEBPA_HUMAN there are 13 pathogenic changes around while only 0 benign (100%) in NM_004364.5
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_004364.5.
PP5
?
Variant 19-33301423-A-AGCTGTTCCACCCGCTTGCGCAGGCGGTCATTGTCACTGGTCAGCTCCAGCACCTTCT is Pathogenic according to our data. Variant chr19-33301423-A-AGCTGTTCCACCCGCTTGCGCAGGCGGTCATTGTCACTGGTCAGCTCCAGCACCTTCT is described in ClinVar as [Pathogenic]. Clinvar id is 17569.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEBPA | NM_004364.5 | c.991_992insAGAAGGTGCTGGAGCTGACCAGTGACAATGACCGCCTGCGCAAGCGGGTGGAACAGC | p.Gln312_Gln330dup | inframe_insertion | 1/1 | ENST00000498907.3 | |
CEBPA | NM_001285829.2 | c.634_635insAGAAGGTGCTGGAGCTGACCAGTGACAATGACCGCCTGCGCAAGCGGGTGGAACAGC | p.Gln193_Gln211dup | inframe_insertion | 1/1 | ||
CEBPA | NM_001287424.2 | c.1096_1097insAGAAGGTGCTGGAGCTGACCAGTGACAATGACCGCCTGCGCAAGCGGGTGGAACAGC | p.Gln347_Gln365dup | inframe_insertion | 1/1 | ||
CEBPA | NM_001287435.2 | c.949_950insAGAAGGTGCTGGAGCTGACCAGTGACAATGACCGCCTGCGCAAGCGGGTGGAACAGC | p.Gln298_Gln316dup | inframe_insertion | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEBPA | ENST00000498907.3 | c.991_992insAGAAGGTGCTGGAGCTGACCAGTGACAATGACCGCCTGCGCAAGCGGGTGGAACAGC | p.Gln312_Gln330dup | inframe_insertion | 1/1 | NM_004364.5 | P1 | ||
ENST00000587312.1 | n.150_206dup | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Acute myeloid leukemia Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2003 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at