19-33379408-C-T

Position:

• chr19-33379408-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001806.4(CEBPG):​c.169C>T​(p.Pro57Ser) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CEBPG NM_001806.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.888

Genes affected

CEBPG (HGNC:1837): (CCAAT enhancer binding protein gamma) The C/EBP family of transcription factors regulates viral and cellular CCAAT/enhancer element-mediated transcription. C/EBP proteins contain the bZIP region, which is characterized by two motifs in the C-terminal half of the protein: a basic region involved in DNA binding and a leucine zipper motif involved in dimerization. The C/EBP family consist of several related proteins, C/EBP alpha, C/EBP beta, C/EBP gamma, and C/EBP delta, that form homodimers and that form heterodimers with each other. CCAAT/enhancer binding protein gamma may cooperate with Fos to bind PRE-I enhancer elements. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05626279).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEBPG	NM_001806.4	c.169C>T	p.Pro57Ser	missense_variant	2/2	ENST00000284000.9
CEBPG	NM_001252296.2	c.169C>T	p.Pro57Ser	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEBPG	ENST00000284000.9	c.169C>T	p.Pro57Ser	missense_variant	2/2	1	NM_001806.4	P1
CEBPG	ENST00000585933.2	c.169C>T	p.Pro57Ser	missense_variant	2/2	2		P1
CEBPG	ENST00000652630.1	c.169C>T	p.Pro57Ser	missense_variant, NMD_transcript_variant	2/3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.169C>T (p.P57S) alteration is located in exon 2 (coding exon 1) of the CEBPG gene. This alteration results from a C to T substitution at nucleotide position 169, causing the proline (P) at amino acid position 57 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.69
DEOGEN2	Benign	0.072	T;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.19	N
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.056	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.33	N;.
REVEL	Benign	0.044
Sift	Benign	0.21	T;.
Sift4G	Benign	0.75	T;T
Polyphen		0.0	B;B
Vest4		0.039
MutPred		0.31		Gain of phosphorylation at P57 (P = 0.0017);Gain of phosphorylation at P57 (P = 0.0017);
MVP		0.51
MPC		0.056
ClinPred		0.031	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.051
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-33870314; COSMIC: COSV99392849;