rs3745972

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004364.5(CEBPA):c.713C>T(p.Ala238Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000173 in 1,153,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A238G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

CEBPA
NM_004364.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 5.10

Publications

3 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:

ENSG00000267727 (HGNC:):

ENSG00000267727 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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27913475).

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.713C>T	p.Ala238Val	missense	Exon 1 of 1	NP_004355.2
CEBPA	NM_001287424.2		c.818C>T	p.Ala273Val	missense	Exon 1 of 1	NP_001274353.1	P49715-4
CEBPA	NM_001287435.2		c.671C>T	p.Ala224Val	missense	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.713C>T	p.Ala238Val	missense	Exon 1 of 1	ENSP00000427514.1	P49715-1
ENSG00000267727	ENST00000587312.1	TSL:3	n.356+68G>A		intron	N/A
CEBPA-DT	ENST00000718467.1		n.-52G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000673

AC:

AN:

148484

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.95e-7

AC:

AN:

1004724

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

475858

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19990

American (AMR)

AF:

0.00

AC:

AN:

5760

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10438

East Asian (EAS)

AF:

0.00

AC:

AN:

17334

South Asian (SAS)

AF:

0.00

AC:

AN:

19086

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16678

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3244

European-Non Finnish (NFE)

AF:

0.00000114

AC:

AN:

874414

Other (OTH)

AF:

0.00

AC:

AN:

37780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00000673

AC:

AN:

148484

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41058

American (AMR)

AF:

0.00

AC:

AN:

14966

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3418

East Asian (EAS)

AF:

0.00

AC:

AN:

5118

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9168

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

66656

Other (OTH)

AF:

0.00

AC:

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.32

Eigen

Benign

-0.046

Eigen_PC

Benign

-0.024

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

5.1

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.1

REVEL

Benign

0.081

Sift

Benign

0.33

Sift4G

Benign

0.46

Polyphen

0.90

Vest4

0.24

MutPred

0.12

Loss of glycosylation at P239 (P = 0.0959)

MVP

0.30

ClinPred

0.36

GERP RS

4.1

Varity_R

0.096

gMVP

0.35

Mutation Taster

=74/26

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over