rs1060502118
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004364.5(CEBPA):c.595_596delinsTT(p.Ala199Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A199T) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Consequence
CEBPA
NM_004364.5 missense
NM_004364.5 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.22
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEBPA | NM_004364.5 | c.595_596delinsTT | p.Ala199Leu | missense_variant | 1/1 | ENST00000498907.3 | |
CEBPA | NM_001285829.2 | c.238_239delinsTT | p.Ala80Leu | missense_variant | 1/1 | ||
CEBPA | NM_001287424.2 | c.700_701delinsTT | p.Ala234Leu | missense_variant | 1/1 | ||
CEBPA | NM_001287435.2 | c.553_554delinsTT | p.Ala185Leu | missense_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEBPA | ENST00000498907.3 | c.595_596delinsTT | p.Ala199Leu | missense_variant | 1/1 | NM_004364.5 | P1 | ||
ENST00000587312.1 | n.361_362delinsAA | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Acute myeloid leukemia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 15, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 2023 | This variant is also known as 744-745GC>TT. This sequence change replaces alanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 199 of the CEBPA protein (p.Ala199Leu). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individual(s) with acute myeloid leukemia (PMID: 18768433). ClinVar contains an entry for this variant (Variation ID: 408745). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at