rs1357810737
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2
The NM_004364.5(CEBPA):c.787C>T(p.Leu263Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000701 in 1,426,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. 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. L263R) has been classified as Uncertain significance.
Frequency
Consequence
NM_004364.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEBPA | NM_004364.5 | c.787C>T | p.Leu263Phe | missense_variant | 1/1 | ENST00000498907.3 | |
CEBPA | NM_001287424.2 | c.892C>T | p.Leu298Phe | missense_variant | 1/1 | ||
CEBPA | NM_001287435.2 | c.745C>T | p.Leu249Phe | missense_variant | 1/1 | ||
CEBPA | NM_001285829.2 | c.430C>T | p.Leu144Phe | missense_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEBPA | ENST00000498907.3 | c.787C>T | p.Leu263Phe | missense_variant | 1/1 | NM_004364.5 | P1 | ||
ENST00000587312.1 | n.350G>A | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000107 AC: 2AN: 186870Hom.: 0 AF XY: 0.0000194 AC XY: 2AN XY: 103168
GnomAD4 exome AF: 0.00000701 AC: 10AN: 1426970Hom.: 0 Cov.: 31 AF XY: 0.00000989 AC XY: 7AN XY: 708140
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Acute myeloid leukemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 05, 2021 | This sequence change replaces leucine with phenylalanine at codon 263 of the CEBPA protein (p.Leu263Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CEBPA-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at