rs12691

chr19-33300221-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004364.5(CEBPA):c.*1117C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 233,458 control chromosomes in the GnomAD database, including 3,048 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2277 hom., cov: 32)
  • Exomes 𝑓: 0.13 (771 hom.)
• Consequence: CEBPA NM_004364.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEBPA	NM_004364.5	c.*1117C>T		3_prime_UTR_variant	1/1	ENST00000498907.3
CEBPA	NM_001285829.2	c.*1117C>T		3_prime_UTR_variant	1/1
CEBPA	NM_001287424.2	c.*1117C>T		3_prime_UTR_variant	1/1
CEBPA	NM_001287435.2	c.*1117C>T		3_prime_UTR_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEBPA	ENST00000498907.3	c.*1117C>T		3_prime_UTR_variant	1/1		NM_004364.5	P1
	ENST00000589932.1	n.288G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23875 AN: 151996 Hom.: 2264 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.0825

Gnomad FIN AF: 0.0954

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.126 AC: 10226 AN: 81344 Hom.: 771 Cov.: 0 AF XY: 0.125 AC XY: 4688 AN XY: 37434

Gnomad4 AFR exome AF: 0.257

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.0151

Gnomad4 SAS exome AF: 0.0997

Gnomad4 FIN exome AF: 0.0916

Gnomad4 NFE exome AF: 0.141

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.157 AC: 23918 AN: 152114 Hom.: 2277 Cov.: 32 AF XY: 0.153 AC XY: 11371 AN XY: 74344

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.00988

Gnomad4 SAS AF: 0.0834

Gnomad4 FIN AF: 0.0954

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.152

Alfa AF: 0.142 Hom.: 1242

Bravo AF: 0.163

Asia WGS AF: 0.0530 AC: 187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	10
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs12691; hg19: chr19-33791127;