GeneBe

19-33302019-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_004364.5(CEBPA):​c.396C>A​(p.Gly132Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000969 in 1,032,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G132G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 9.7e-7 ( 0 hom. )

Consequence

CEBPA
NM_004364.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.12

Publications

0 publications found
Variant links:
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: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP7
Synonymous conserved (PhyloP=3.12 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CEBPANM_004364.5 linkc.396C>A p.Gly132Gly synonymous_variant Exon 1 of 1 ENST00000498907.3 NP_004355.2 P49715-1
CEBPANM_001287424.2 linkc.501C>A p.Gly167Gly synonymous_variant Exon 1 of 1 NP_001274353.1 P49715-4
CEBPANM_001287435.2 linkc.354C>A p.Gly118Gly synonymous_variant Exon 1 of 1 NP_001274364.1 P49715-2
CEBPANM_001285829.2 linkc.39C>A p.Gly13Gly synonymous_variant Exon 1 of 1 NP_001272758.1 P49715-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CEBPAENST00000498907.3 linkc.396C>A p.Gly132Gly synonymous_variant Exon 1 of 1 6 NM_004364.5 ENSP00000427514.1 P49715-1
CEBPA-DTENST00000718467.1 linkn.46+220G>T intron_variant Intron 1 of 1
ENSG00000267727ENST00000587312.1 linkn.*79G>T downstream_gene_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
9.69e-7
AC:
1
AN:
1032134
Hom.:
0
Cov.:
33
AF XY:
0.00000205
AC XY:
1
AN XY:
487844
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
20680
American (AMR)
AF:
0.00
AC:
0
AN:
6550
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
11616
East Asian (EAS)
AF:
0.00
AC:
0
AN:
21346
South Asian (SAS)
AF:
0.00
AC:
0
AN:
20202
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
22758
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2612
European-Non Finnish (NFE)
AF:
0.00000113
AC:
1
AN:
886940
Other (OTH)
AF:
0.00
AC:
0
AN:
39430
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
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
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
CADD
Benign
11
DANN
Benign
0.87
PhyloP100
3.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1060504475; hg19: chr19-33792925; API