chr19-33379349-C-T

Position:

• chr19-33379349-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000284000.9(CEBPG):​c.110C>T​(p.Ala37Val) 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. 13/21 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 ENST00000284000.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.17

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07392344).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEBPG	NM_001806.4	c.110C>T	p.Ala37Val	missense_variant	2/2	ENST00000284000.9	NP_001797.1
CEBPG	NM_001252296.2	c.110C>T	p.Ala37Val	missense_variant	2/2		NP_001239225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEBPG	ENST00000284000.9	c.110C>T	p.Ala37Val	missense_variant	2/2	1	NM_001806.4	ENSP00000284000	P1
CEBPG	ENST00000585933.2	c.110C>T	p.Ala37Val	missense_variant	2/2	2		ENSP00000466022	P1
CEBPG	ENST00000652630.1	c.110C>T	p.Ala37Val	missense_variant, NMD_transcript_variant	2/3			ENSP00000499062

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

Apr 04, 2023

The c.110C>T (p.A37V) 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 110, causing the alanine (A) at amino acid position 37 to be replaced by a valine (V). 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	0.081
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.085	T;T
Eigen	Benign	-0.20
Eigen_PC	Benign	0.063
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.80	.;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.074	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N;N
MutationTaster	Benign	0.70	D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.81	N;.
REVEL	Benign	0.079
Sift	Benign	0.37	T;.
Sift4G	Benign	0.34	T;T
Polyphen		0.0010	B;B
Vest4		0.048
MutPred		0.084		Loss of glycosylation at P39 (P = 0.2135);Loss of glycosylation at P39 (P = 0.2135);
MVP		0.60
MPC		0.055
ClinPred		0.51	D
GERP RS		4.8
Varity_R		0.080
gMVP		0.59

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: chr19-33870255;