rs1213133617

Variant names:

• chr19-33301719-C-A
• rs1213133617
• NM_004364.5:c.696G>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_004364.5(CEBPA):​c.696G>T​(p.Val232Val) 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 147,856 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CEBPA NM_004364.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.38
• 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]

ENSG00000267727 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 19-33301719-C-A is Benign according to our data. Variant chr19-33301719-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 456700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.38 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPA	NM_004364.5	MANE Select	c.696G>T	p.Val232Val	synonymous	Exon 1 of 1	NP_004355.2
	CEBPA	NM_001287424.2		c.801G>T	p.Val267Val	synonymous	Exon 1 of 1	NP_001274353.1
	CEBPA	NM_001287435.2		c.654G>T	p.Val218Val	synonymous	Exon 1 of 1	NP_001274364.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPA	ENST00000498907.3	TSL:6 MANE Select	c.696G>T	p.Val232Val	synonymous	Exon 1 of 1	ENSP00000427514.1
	ENSG00000267727	ENST00000587312.1	TSL:3	n.356+85C>A		intron	N/A
	CEBPA-DT	ENST00000718467.1		n.-35C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.00000676 AC: 1 AN: 147856 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: 0.0000150

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 1786 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000499 AC: 5 AN: 1002096 Hom.: 0 Cov.: 29 AF XY: 0.00000422 AC XY: 2 AN XY: 474160

African (AFR) AF: 0.00 AC: 0 AN: 19942

American (AMR) AF: 0.00 AC: 0 AN: 5720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10428

East Asian (EAS) AF: 0.00 AC: 0 AN: 17720

South Asian (SAS) AF: 0.00 AC: 0 AN: 19136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16698

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2852

European-Non Finnish (NFE) AF: 0.00000573 AC: 5 AN: 871994

Other (OTH) AF: 0.00 AC: 0 AN: 37606

GnomAD4 genome AF: 0.00000676 AC: 1 AN: 147856 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 71972

African (AFR) AF: 0.00 AC: 0 AN: 40872

American (AMR) AF: 0.00 AC: 0 AN: 14914

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3398

East Asian (EAS) AF: 0.00 AC: 0 AN: 5068

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66476

Other (OTH) AF: 0.00 AC: 0 AN: 2034

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Acute myeloid leukemia (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.3
DANN	Benign	0.78
PhyloP100		1.4

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: rs1213133617; hg19: chr19-33792625;