rs779373951

Variant names:

• chr19-33301956-C-G
• rs779373951
• NM_004364.5:c.459G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-33301956-C-G
• chr19-33301956-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_004364.5(CEBPA):​c.459G>C​(p.Pro153Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000676 in 147,976 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P153P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CEBPA NM_004364.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 19-33301956-C-G is Benign according to our data. Variant chr19-33301956-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1114260.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004364.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPA	NM_004364.5	MANE Select	c.459G>C	p.Pro153Pro	synonymous	Exon 1 of 1	NP_004355.2
	CEBPA	NM_001287424.2		c.564G>C	p.Pro188Pro	synonymous	Exon 1 of 1	NP_001274353.1	P49715-4
	CEBPA	NM_001287435.2		c.417G>C	p.Pro139Pro	synonymous	Exon 1 of 1	NP_001274364.1	P49715-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPA	ENST00000498907.3	TSL:6 MANE Select	c.459G>C	p.Pro153Pro	synonymous	Exon 1 of 1	ENSP00000427514.1	P49715-1
	CEBPA-DT	ENST00000718467.1		n.46+157C>G		intron	N/A
	ENSG00000267727	ENST00000587312.1	TSL:3	n.*16C>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.00000676 AC: 1 AN: 147976 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1028282 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 495226

African (AFR) AF: 0.00 AC: 0 AN: 19432

American (AMR) AF: 0.00 AC: 0 AN: 7152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10754

East Asian (EAS) AF: 0.00 AC: 0 AN: 18060

South Asian (SAS) AF: 0.00 AC: 0 AN: 31536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18732

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2482

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 882704

Other (OTH) AF: 0.00 AC: 0 AN: 37430

GnomAD4 genome AF: 0.00000676 AC: 1 AN: 147976 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 72076

African (AFR) AF: 0.00 AC: 0 AN: 40986

American (AMR) AF: 0.00 AC: 0 AN: 14950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.00 AC: 0 AN: 5010

South Asian (SAS) AF: 0.00 AC: 0 AN: 4774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000151 AC: 1 AN: 66346

Other (OTH) AF: 0.00 AC: 0 AN: 2048

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Acute myeloid leukemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.5
DANN	Benign	0.87
PhyloP100		-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

Other links and lift over

dbSNP: rs779373951; hg19: chr19-33792862;