rs1060504477

Variant names:

• chr19-33302028-G-A
• rs1060504477
• NM_004364.5:c.387C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-33302028-G-A
• chr19-33302028-G-C
• chr19-33302028-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6 BP7

The NM_004364.5(CEBPA):​c.387C>T​(p.Pro129Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. P129P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CEBPA NM_004364.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.642
• Publications: 0 publications found

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-DT (HGNC:25710): (CEBPA divergent transcript)

ENSG00000267727 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 19-33302028-G-A is Benign according to our data. Variant chr19-33302028-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3053984.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.642 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEBPA	NM_004364.5	c.387C>T	p.Pro129Pro	synonymous_variant	Exon 1 of 1	ENST00000498907.3	NP_004355.2
CEBPA	NM_001287424.2	c.492C>T	p.Pro164Pro	synonymous_variant	Exon 1 of 1		NP_001274353.1
CEBPA	NM_001287435.2	c.345C>T	p.Pro115Pro	synonymous_variant	Exon 1 of 1		NP_001274364.1
CEBPA	NM_001285829.2	c.30C>T	p.Pro10Pro	synonymous_variant	Exon 1 of 1		NP_001272758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEBPA	ENST00000498907.3	c.387C>T	p.Pro129Pro	synonymous_variant	Exon 1 of 1	6	NM_004364.5	ENSP00000427514.1
CEBPA-DT	ENST00000718467.1	n.46+229G>A		intron_variant	Intron 1 of 1
ENSG00000267727	ENST00000587312.1	n.*88G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1033418 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 488366

African (AFR) AF: 0.00 AC: 0 AN: 20680

American (AMR) AF: 0.00 AC: 0 AN: 6566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11646

East Asian (EAS) AF: 0.00 AC: 0 AN: 21330

South Asian (SAS) AF: 0.00 AC: 0 AN: 20018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2618

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 887200

Other (OTH) AF: 0.00 AC: 0 AN: 39518

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CEBPA-related disorder Benign:1

Dec 06, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.5
DANN	Benign	0.96
PhyloP100		-0.64

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

Other links and lift over

dbSNP: rs1060504477; hg19: chr19-33792934;