rs34529039

Positions:

chr19-33301725-C-A

Variant summary

Our verdict is Benign. Variant got -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:7

Conservation

PhyloP100: -0.0510

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 21402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-33301725-C-A is described in Lovd as [Benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEBPA	NM_004364.5 linkuse as main transcript	c.690G>T	p.Thr230Thr	synonymous_variant	1/1	ENST00000498907.3	NP_004355.2	P49715-1
CEBPA	NM_001287424.2 linkuse as main transcript	c.795G>T	p.Thr265Thr	synonymous_variant	1/1		NP_001274353.1	P49715-4
CEBPA	NM_001287435.2 linkuse as main transcript	c.648G>T	p.Thr216Thr	synonymous_variant	1/1		NP_001274364.1	P49715-2
CEBPA	NM_001285829.2 linkuse as main transcript	c.333G>T	p.Thr111Thr	synonymous_variant	1/1		NP_001272758.1	P49715-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEBPA	ENST00000498907.3 linkuse as main transcript	c.690G>T	p.Thr230Thr	synonymous_variant	1/1	6	NM_004364.5	ENSP00000427514.1		P49715-1
ENSG00000267727	ENST00000587312.1 linkuse as main transcript	n.357-90C>A		intron_variant		3

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

GnomAD3 exomes

AF:

0.186

AC:

255

AN:

1372

Hom.:

AF XY:

0.203

AC XY:

154

AN XY:

760

show subpopulations

Gnomad AFR exome

AF:

0.357

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.100

Gnomad SAS exome

AF:

0.00

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

Gnomad4 AFR exome

AF:

0.267

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.136

Gnomad4 EAS exome

AF:

0.0148

Gnomad4 SAS exome

AF:

0.0864

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

AF:

0.158

AC:

23353

AN:

147850

Hom.:

2221

Cov.:

AF XY:

0.154

AC XY:

11068

AN XY:

72048

show subpopulations

Gnomad4 AFR

AF:

0.253

Gnomad4 AMR

AF:

0.117

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.00987

Gnomad4 SAS

AF:

0.0831

Gnomad4 FIN

AF:

0.0963

Gnomad4 NFE

AF:

0.136

Gnomad4 OTH

AF:

0.153

Alfa

AF:

0.144

Hom.:

231

Bravo

AF:

0.160

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 14, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 16, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Acute myeloid leukemia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	Dec 19, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 18, 2024

This alteration is classified as 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.3

DANN

Benign

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over