19-33301036-G-A

Variant names:

• chr19-33301036-G-A
• rs4142943
• NM_004364.5:c.*302C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004364.5(CEBPA):​c.*302C>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 0.0151 in 502,302 control chromosomes in the GnomAD database, including 520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0092 (106 hom., cov: 32)
  • Exomes 𝑓: 0.018 (414 hom.)
• Consequence: CEBPA NM_004364.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.28

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]

ENSG00000267580 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 19-33301036-G-A is Benign according to our data. Variant chr19-33301036-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1187270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEBPA	NM_004364.5	c.*302C>T		3_prime_UTR_variant	Exon 1 of 1	ENST00000498907.3	NP_004355.2
CEBPA	NM_001287424.2	c.*302C>T		3_prime_UTR_variant	Exon 1 of 1		NP_001274353.1
CEBPA	NM_001287435.2	c.*302C>T		3_prime_UTR_variant	Exon 1 of 1		NP_001274364.1
CEBPA	NM_001285829.2	c.*302C>T		3_prime_UTR_variant	Exon 1 of 1		NP_001272758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEBPA	ENST00000498907	c.*302C>T		3_prime_UTR_variant	Exon 1 of 1		NM_004364.5	ENSP00000427514.1
ENSG00000267580	ENST00000589932.1	n.542-15G>A		intron_variant	Intron 1 of 1	2
ENSG00000267727	ENST00000587312.1	n.-243G>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00920 AC: 1400 AN: 152194 Hom.: 102 Cov.: 32

Gnomad AFR AF: 0.00137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00798

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.0614

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00909

GnomAD4 exome AF: 0.0176 AC: 6173 AN: 349990 Hom.: 414 Cov.: 3 AF XY: 0.0184 AC XY: 3329 AN XY: 180440

Gnomad4 AFR exome AF: 0.00200 AC: 22 AN: 11026

Gnomad4 AMR exome AF: 0.00709 AC: 108 AN: 15238

Gnomad4 ASJ exome AF: 0.00404 AC: 46 AN: 11398

Gnomad4 EAS exome AF: 0.157 AC: 4013 AN: 25492

Gnomad4 SAS exome AF: 0.0494 AC: 1549 AN: 31366

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 22450

Gnomad4 NFE exome AF: 0.000338 AC: 71 AN: 210224

Gnomad4 Remaining exome AF: 0.0170 AC: 361 AN: 21186

GnomAD4 genome AF: 0.00923 AC: 1406 AN: 152312 Hom.: 106 Cov.: 32 AF XY: 0.0110 AC XY: 818 AN XY: 74476

Gnomad4 AFR AF: 0.00137 AC: 0.00137092 AN: 0.00137092

Gnomad4 AMR AF: 0.00791 AC: 0.0079054 AN: 0.0079054

Gnomad4 ASJ AF: 0.00346 AC: 0.00345622 AN: 0.00345622

Gnomad4 EAS AF: 0.170 AC: 0.169636 AN: 0.169636

Gnomad4 SAS AF: 0.0602 AC: 0.0602235 AN: 0.0602235

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000191 AC: 0.00019112 AN: 0.00019112

Gnomad4 OTH AF: 0.0170 AC: 0.0170455 AN: 0.0170455

Alfa AF: 0.00935 Hom.: 67

Bravo AF: 0.00893

Asia WGS AF: 0.147 AC: 508 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 24, 2019

GeneDx

Significance: Likely 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	-0.55
CADD	Benign	18
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs4142943; hg19: chr19-33791942;