rs3745968

Positions:

• chr19-33381504-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001806.4(CEBPG):​c.*1812A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.096 in 167,018 control chromosomes in the GnomAD database, including 857 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.096 (769 hom., cov: 33)
  • Exomes 𝑓: 0.10 (88 hom.)
• Consequence: CEBPG NM_001806.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.569

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEBPG	NM_001806.4	c.*1812A>G		3_prime_UTR_variant	2/2	ENST00000284000.9	NP_001797.1
CEBPG	NM_001252296.2	c.*1812A>G		3_prime_UTR_variant	2/2		NP_001239225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEBPG	ENST00000284000.9	c.*1812A>G		3_prime_UTR_variant	2/2	1	NM_001806.4	ENSP00000284000	P1
CEBPG	ENST00000585933.2	c.*1812A>G		3_prime_UTR_variant	2/2	2		ENSP00000466022	P1
CEBPG	ENST00000652630.1	c.*884A>G		3_prime_UTR_variant, NMD_transcript_variant	3/3			ENSP00000499062

Frequencies

GnomAD3 genomes AF: 0.0957 AC: 14554 AN: 152104 Hom.: 769 Cov.: 33

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0731

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0173

Gnomad SAS AF: 0.0585

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0923

GnomAD4 exome AF: 0.100 AC: 1483 AN: 14796 Hom.: 88 Cov.: 0 AF XY: 0.0981 AC XY: 690 AN XY: 7034

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome AF: 0.0956 AC: 14558 AN: 152222 Hom.: 769 Cov.: 33 AF XY: 0.0940 AC XY: 6998 AN XY: 74422

Gnomad4 AFR AF: 0.0847

Gnomad4 AMR AF: 0.0730

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.0172

Gnomad4 SAS AF: 0.0594

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.0914

Alfa AF: 0.107 Hom.: 1310

Bravo AF: 0.0944

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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

Publications

LitVar

Other links and lift over

dbSNP: rs3745968; hg19: chr19-33872410; COSMIC: COSV52287683;