dbSNP rs34529039: CEBPA:p.Thr230Thr (chr19-33301725-C-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004364.5(CEBPA):c.690G>T(p.Thr230Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,149,514 control chromosomes in the GnomAD database, including 12,241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2221 hom., cov: 32)

Exomes 𝑓: 0.14 ( 10020 hom. )

Consequence

CEBPA
NM_004364.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0510

Publications

18 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

new If you want to explore the variant's impact on the transcript NM_004364.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 19-33301725-C-A is Benign according to our data. Variant chr19-33301725-C-A is described in ClinVar as Benign. ClinVar VariationId is 21402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.051 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

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.690G>T	p.Thr230Thr	synonymous	Exon 1 of 1	NP_004355.2
CEBPA	NM_001287424.2		c.795G>T	p.Thr265Thr	synonymous	Exon 1 of 1	NP_001274353.1	P49715-4
CEBPA	NM_001287435.2		c.648G>T	p.Thr216Thr	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.690G>T	p.Thr230Thr	synonymous	Exon 1 of 1	ENSP00000427514.1	P49715-1
ENSG00000267727	ENST00000587312.1	TSL:3	n.357-90C>A		intron	N/A
CEBPA-DT	ENST00000718467.1		n.-29C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

23314

AN:

147742

Hom.:

2208

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.0996

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.0100

Gnomad SAS

AF:

0.0822

Gnomad FIN

AF:

0.0963

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.155

GnomAD2 exomes

AF:

0.186

AC:

255

AN:

1372

AF XY:

0.203

show subpopulations

Gnomad AFR exome

AF:

0.357

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.100

Gnomad FIN exome

AF:

0.149

Gnomad NFE exome

AF:

0.196

Gnomad OTH exome

AF:

0.176

GnomAD4 exome

AF:

0.138

AC:

138024

AN:

1001664

Hom.:

10020

Cov.:

AF XY:

0.137

AC XY:

65049

AN XY:

473778

show subpopulations

African (AFR)

AF:

0.267

AC:

5334

AN:

19994

American (AMR)

AF:

0.111

AC:

640

AN:

5746

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

1423

AN:

10492

East Asian (EAS)

AF:

0.0148

AC:

268

AN:

18130

South Asian (SAS)

AF:

0.0864

AC:

1667

AN:

19302

European-Finnish (FIN)

AF:

0.104

AC:

1744

AN:

16750

Middle Eastern (MID)

AF:

0.178

AC:

477

AN:

2680

European-Non Finnish (NFE)

AF:

0.139

AC:

121381

AN:

871034

Other (OTH)

AF:

0.136

AC:

5090

AN:

37536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

5715

11430

17145

22860

28575

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5228

10456

15684

20912

26140

<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:

0.158

AC:

23353

AN:

147850

Hom.:

2221

Cov.:

AF XY:

0.154

AC XY:

11068

AN XY:

72048

show subpopulations

African (AFR)

AF:

0.253

AC:

10351

AN:

40910

American (AMR)

AF:

0.117

AC:

1739

AN:

14918

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

448

AN:

3402

East Asian (EAS)

AF:

0.00987

AC:

AN:

5068

South Asian (SAS)

AF:

0.0831

AC:

398

AN:

4790

European-Finnish (FIN)

AF:

0.0963

AC:

871

AN:

9040

Middle Eastern (MID)

AF:

0.155

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.136

AC:

9047

AN:

66472

Other (OTH)

AF:

0.153

AC:

314

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

957

1914

2870

3827

4784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<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:

0.144

Hom.:

231

Bravo

AF:

0.160

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Acute myeloid leukemia (2)

not specified (2)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.3

(source)

DANN

Benign

0.79

PhyloP100

-0.051

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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