20-50191611-C-A

Variant names:

• chr20-50191611-C-A
• rs886887483
• NM_005194.4:c.578C>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005194.4(CEBPB):​c.578C>A​(p.Pro193Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000922 in 1,193,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000092 (0 hom.)
• Consequence: CEBPB NM_005194.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379

Genes affected

CEBPB (HGNC:1834): (CCAAT enhancer binding protein beta) This intronless gene encodes a transcription factor that contains a basic leucine zipper (bZIP) domain. The encoded protein functions as a homodimer but can also form heterodimers with CCAAT/enhancer-binding proteins alpha, delta, and gamma. Activity of this protein is important in the regulation of genes involved in immune and inflammatory responses, among other processes. The use of alternative in-frame AUG start codons results in multiple protein isoforms, each with distinct biological functions. [provided by RefSeq, Oct 2013]

CEBPB-AS1 (HGNC:51226): (CEBPB antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22636735).
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEBPB	NM_005194.4	c.578C>A	p.Pro193Gln	missense_variant	Exon 1 of 1	ENST00000303004.5	NP_005185.2
CEBPB	NM_001285878.1	c.509C>A	p.Pro170Gln	missense_variant	Exon 1 of 1		NP_001272807.1
CEBPB	NM_001285879.1	c.-17C>A		5_prime_UTR_variant	Exon 1 of 1		NP_001272808.1
CEBPB-AS1	NR_125739.1	n.406+53G>T		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEBPB	ENST00000303004.5	c.578C>A	p.Pro193Gln	missense_variant	Exon 1 of 1	6	NM_005194.4	ENSP00000305422.3
CEBPB-AS1	ENST00000613921.1	n.-113G>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.000104 AC: 2 AN: 19196 Hom.: 0 AF XY: 0.0000796 AC XY: 1 AN XY: 12556

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000922 AC: 11 AN: 1193102 Hom.: 0 Cov.: 34 AF XY: 0.0000120 AC XY: 7 AN XY: 581240

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 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000111

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.087
Sift	Benign	0.23	T
Sift4G	Benign	0.44	T
Polyphen		0.94	P
Vest4		0.16
MutPred		0.22		Gain of solvent accessibility (P = 0.1505);
MVP		0.73
MPC		1.3
ClinPred		0.31	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.12
gMVP		0.25

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: rs886887483; hg19: chr20-48808148;