Genetic Variant CEBPA:p.Pro129Pro (chr19-33302028-G-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004364.5(CEBPA):c.387C>A(p.Pro129Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000761 in 1,182,176 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P129P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

CEBPA
NM_004364.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 19-33302028-G-T is Benign according to our data. Variant chr19-33302028-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 706391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

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

BS2

High AC in GnomAd4 at 6 AD gene.

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	UniProt
CEBPA	NM_004364.5	MANE Select	c.387C>A	p.Pro129Pro	synonymous	Exon 1 of 1	NP_004355.2
CEBPA	NM_001287424.2		c.492C>A	p.Pro164Pro	synonymous	Exon 1 of 1	NP_001274353.1	P49715-4
CEBPA	NM_001287435.2		c.345C>A	p.Pro115Pro	synonymous	Exon 1 of 1	NP_001274364.1	P49715-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEBPA	ENST00000498907.3	TSL:6 MANE Select	c.387C>A	p.Pro129Pro	synonymous	Exon 1 of 1	ENSP00000427514.1	P49715-1
CEBPA-DT	ENST00000718467.1		n.46+229G>T		intron	N/A
ENSG00000267727	ENST00000587312.1	TSL:3	n.*88G>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000403

AC:

AN:

148758

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000666

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000290

AC:

AN:

1033418

Hom.:

Cov.:

AF XY:

0.00000410

AC XY:

AN XY:

488366

show subpopulations

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:

0.00000338

AC:

AN:

887200

Other (OTH)

AF:

0.00

AC:

AN:

39518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000403

AC:

AN:

148758

Hom.:

Cov.:

AF XY:

0.0000690

AC XY:

AN XY:

72500

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

41022

American (AMR)

AF:

0.0000666

AC:

AN:

15004

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3418

East Asian (EAS)

AF:

0.00

AC:

AN:

5038

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66860

Other (OTH)

AF:

0.00

AC:

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000416

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Acute myeloid leukemia (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.9

(source)

DANN

Benign

0.92

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over