Genetic Variant CEBPA:p.Pro129Pro (chr19-33302028-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The NM_004364.5(CEBPA):c.387C>T(p.Pro129Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. P129P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CEBPA
NM_004364.5 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.642

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 links:

CEBPA-DT (HGNC:25710): (CEBPA divergent transcript)

CEBPA-DT links:

ENSG00000267727 (HGNC:):

ENSG00000267727 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 19-33302028-G-A is Benign according to our data. Variant chr19-33302028-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3053984.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.642 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004364.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CEBPA	NM_004364.5	MANE Select	c.387C>T	p.Pro129Pro	synonymous	Exon 1 of 1	NP_004355.2
CEBPA	NM_001287424.2		c.492C>T	p.Pro164Pro	synonymous	Exon 1 of 1	NP_001274353.1
CEBPA	NM_001287435.2		c.345C>T	p.Pro115Pro	synonymous	Exon 1 of 1	NP_001274364.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CEBPA	ENST00000498907.3	TSL:6 MANE Select	c.387C>T	p.Pro129Pro	synonymous	Exon 1 of 1	ENSP00000427514.1
CEBPA-DT	ENST00000718467.1		n.46+229G>A		intron	N/A
ENSG00000267727	ENST00000587312.1	TSL:3	n.*88G>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1033418

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

488366

African (AFR)

AF:

0.00

AC:

AN:

20680

American (AMR)

AF:

0.00

AC:

AN:

6566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11646

East Asian (EAS)

AF:

0.00

AC:

AN:

21330

South Asian (SAS)

AF:

0.00

AC:

AN:

20018

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23842

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2618

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

887200

Other (OTH)

AF:

0.00

AC:

AN:

39518

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CEBPA-related disorder

Benign:1

Dec 06, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.5

(source)

DANN

Benign

0.96

PhyloP100

-0.64

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over