Genetic Variant CEBPA:p.Pro14Ser (chr19-33302375-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004364.5(CEBPA):c.40C>T(p.Pro14Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000173 in 1,155,772 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P14L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000017 ( 1 hom. )

Consequence

CEBPA
NM_004364.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.40

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12234005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEBPA	NM_004364.5 link	c.40C>T	p.Pro14Ser	missense_variant	Exon 1 of 1	ENST00000498907.3	NP_004355.2	P49715-1
CEBPA	NM_001287424.2 link	c.145C>T	p.Pro49Ser	missense_variant	Exon 1 of 1		NP_001274353.1	P49715-4
CEBPA	NM_001287435.2 link	c.-3C>T		5_prime_UTR_variant	Exon 1 of 1		NP_001274364.1	P49715-2
CEBPA	NM_001285829.2 link	c.-318C>T		5_prime_UTR_variant	Exon 1 of 1		NP_001272758.1	P49715-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEBPA	ENST00000498907.3 link	c.40C>T	p.Pro14Ser	missense_variant	Exon 1 of 1	6	NM_004364.5	ENSP00000427514.1		P49715-1
CEBPA-DT	ENST00000718467.1 link	n.46+576G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000173

AC:

AN:

1155772

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

556836

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23082

American (AMR)

AF:

0.00

AC:

AN:

8478

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14964

East Asian (EAS)

AF:

0.00

AC:

AN:

26796

South Asian (SAS)

AF:

0.00

AC:

AN:

35258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37304

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4174

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

959456

Other (OTH)

AF:

0.0000432

AC:

AN:

46260

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.22

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.18

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.63

M_CAP

Pathogenic

0.61

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

PhyloP100

5.4

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.1

REVEL

Benign

0.081

Sift

Benign

0.59

Sift4G

Benign

0.69

Polyphen

0.028

Vest4

0.15

MutPred

0.14

Gain of phosphorylation at P14 (P = 0.0041);

MVP

0.27

ClinPred

0.26

GERP RS

4.1

PromoterAI

-0.060

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.084

gMVP

0.41

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over