rs571969199

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_004364.5(CEBPA):c.756G>T(p.Ala252Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,488,680 control chromosomes in the GnomAD database, including 26 homozygotes. 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. A252A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0071 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00083 ( 12 hom. )

Consequence

CEBPA
NM_004364.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0550

Publications

2 publications found

Variant links:

COSMIC-nc: COSV105200112

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: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 19-33301659-C-A is Benign according to our data. Variant chr19-33301659-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 415189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.055 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00708 (1061/149830) while in subpopulation AFR AF = 0.0245 (1011/41270). AF 95% confidence interval is 0.0232. There are 14 homozygotes in GnomAd4. There are 504 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1061 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEBPA	NM_004364.5 link	c.756G>T	p.Ala252Ala	synonymous_variant	Exon 1 of 1	ENST00000498907.3	NP_004355.2	P49715-1
CEBPA	NM_001287424.2 link	c.861G>T	p.Ala287Ala	synonymous_variant	Exon 1 of 1		NP_001274353.1	P49715-4
CEBPA	NM_001287435.2 link	c.714G>T	p.Ala238Ala	synonymous_variant	Exon 1 of 1		NP_001274364.1	P49715-2
CEBPA	NM_001285829.2 link	c.399G>T	p.Ala133Ala	synonymous_variant	Exon 1 of 1		NP_001272758.1	P49715-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CEBPA	ENST00000498907.3 link	c.756G>T	p.Ala252Ala	synonymous_variant	Exon 1 of 1	6	NM_004364.5	ENSP00000427514.1	P49715-1
ENSG00000267727	ENST00000587312.1 link	n.356+25C>A		intron_variant	Intron 1 of 1	3
CEBPA-DT	ENST00000718467.1 link	n.-95C>A		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.00707

AC:

1058

AN:

149722

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00193

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000149

Gnomad OTH

AF:

0.00389

GnomAD2 exomes

AF:

0.00183

AC:

176

AN:

96236

AF XY:

0.00150

show subpopulations

Gnomad AFR exome

AF:

0.0600

Gnomad AMR exome

AF:

0.00149

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000320

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.000830

AC:

1111

AN:

1338850

Hom.:

Cov.:

AF XY:

0.000756

AC XY:

499

AN XY:

659876

show subpopulations

African (AFR)

AF:

0.0296

AC:

824

AN:

27862

American (AMR)

AF:

0.00170

AC:

AN:

30612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22908

East Asian (EAS)

AF:

0.00

AC:

AN:

31574

South Asian (SAS)

AF:

0.000189

AC:

AN:

74126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36146

Middle Eastern (MID)

AF:

0.00165

AC:

AN:

5470

European-Non Finnish (NFE)

AF:

0.0000967

AC:

102

AN:

1054738

Other (OTH)

AF:

0.00199

AC:

110

AN:

55414

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.557

Heterozygous variant carriers

100

151

201

251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00708

AC:

1061

AN:

149830

Hom.:

Cov.:

AF XY:

0.00689

AC XY:

504

AN XY:

73142

show subpopulations

African (AFR)

AF:

0.0245

AC:

1011

AN:

41270

American (AMR)

AF:

0.00193

AC:

AN:

15050

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3440

East Asian (EAS)

AF:

0.00

AC:

AN:

5120

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9588

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000149

AC:

AN:

67256

Other (OTH)

AF:

0.00385

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

104

155

207

259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00335

Hom.:

Bravo

AF:

0.00774

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 22, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 14, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Nov 15, 2018

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Aug 21, 2024

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Acute myeloid leukemia

Benign:1

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

8.8

(source)

DANN

Benign

0.89

PhyloP100

0.055

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over