NM_004364.5:c.51C>A
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_004364.5(CEBPA):c.51C>A(p.Ser17Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000912 in 1,315,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S17G) has been classified as Uncertain significance.
Frequency
Consequence
NM_004364.5 missense
Scores
Clinical Significance
Conservation
Publications
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ACMG classification
Our verdict: Likely_benign. The variant received -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CEBPA | NM_004364.5 | c.51C>A | p.Ser17Arg | missense_variant | Exon 1 of 1 | ENST00000498907.3 | NP_004355.2 | |
CEBPA | NM_001287424.2 | c.156C>A | p.Ser52Arg | missense_variant | Exon 1 of 1 | NP_001274353.1 | ||
CEBPA | NM_001287435.2 | c.9C>A | p.Ser3Arg | missense_variant | Exon 1 of 1 | NP_001274364.1 | ||
CEBPA | NM_001285829.2 | c.-307C>A | 5_prime_UTR_variant | Exon 1 of 1 | NP_001272758.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000660 AC: 1AN: 151424Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000909 AC: 1AN: 10996 AF XY: 0.000181 show subpopulations
GnomAD4 exome AF: 0.00000945 AC: 11AN: 1164040Hom.: 0 Cov.: 32 AF XY: 0.0000107 AC XY: 6AN XY: 562158 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00000660 AC: 1AN: 151424Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73934 show subpopulations
ClinVar
Submissions by phenotype
Acute myeloid leukemia Uncertain:1
This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 17 of the CEBPA protein (p.Ser17Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CEBPA-related conditions. ClinVar contains an entry for this variant (Variation ID: 456689). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CEBPA protein function with a negative predictive value of 80%. 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