rs2081577990

Variant names:

• chr20-50191538-C-A
• NM_005194.4:c.505C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-50191538-C-A
• chr20-50191538-C-T

Variant summary

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

The NM_005194.4(CEBPB):​c.505C>A​(p.Pro169Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000086 in 1,162,710 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: 8.6e-7 (0 hom.)
• Consequence: CEBPB NM_005194.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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 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=0.26385325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEBPB	NM_005194.4	c.505C>A	p.Pro169Thr	missense_variant	Exon 1 of 1	ENST00000303004.5	NP_005185.2
CEBPB	NM_001285878.1	c.436C>A	p.Pro146Thr	missense_variant	Exon 1 of 1		NP_001272807.1
CEBPB	NM_001285879.1	c.-90C>A		5_prime_UTR_variant	Exon 1 of 1		NP_001272808.1
CEBPB-AS1	NR_125739.1	n.407-116G>T		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEBPB	ENST00000303004.5	c.505C>A	p.Pro169Thr	missense_variant	Exon 1 of 1	6	NM_005194.4	ENSP00000305422.3
CEBPB-AS1	ENST00000613921.1	n.-40G>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.60e-7 AC: 1 AN: 1162710 Hom.: 0 Cov.: 33 AF XY: 0.00000177 AC XY: 1 AN XY: 564416

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: 0.0000259

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.41	T
M_CAP	Pathogenic	0.90	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.1	L
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.19
Sift	Benign	0.15	T
Sift4G	Benign	0.56	T
Polyphen		0.18	B
Vest4		0.18
MutPred		0.33		Gain of phosphorylation at P169 (P = 0.0025);
MVP		0.94
MPC		1.5
ClinPred		0.19	T
GERP RS		2.4
Varity_R		0.22
gMVP		0.27

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: chr20-48808075;