Genetic Variant NM_005194.4:c.275C>G (chr20-50191308-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005194.4(CEBPB):c.275C>G(p.Thr92Arg) 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. 14/22 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)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CEBPB
NM_005194.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77

Publications

0 publications found

Variant links:

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 links:

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

CEBPB-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13075572).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005194.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEBPB	NM_005194.4	MANE Select	c.275C>G	p.Thr92Arg	missense	Exon 1 of 1	NP_005185.2
CEBPB	NM_001285878.1		c.206C>G	p.Thr69Arg	missense	Exon 1 of 1	NP_001272807.1	P17676-2
CEBPB	NM_001285879.1		c.-320C>G		5_prime_UTR	Exon 1 of 1	NP_001272808.1	P17676-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEBPB	ENST00000303004.5	TSL:6 MANE Select	c.275C>G	p.Thr92Arg	missense	Exon 1 of 1	ENSP00000305422.3	P17676-1
CEBPB	ENST00000718336.1		c.275C>G	p.Thr92Arg	missense	Exon 1 of 1	ENSP00000520773.1	P17676-1
CEBPB-AS1	ENST00000613921.1	TSL:3	n.191G>C		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1204632

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

592030

African (AFR)

AF:

0.00

AC:

AN:

23526

American (AMR)

AF:

0.00

AC:

AN:

15482

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18406

East Asian (EAS)

AF:

0.00

AC:

AN:

24162

South Asian (SAS)

AF:

0.00

AC:

AN:

55322

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4654

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

979480

Other (OTH)

AF:

0.00

AC:

AN:

47490

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.17

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.60

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.48

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

2.8

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.61

REVEL

Benign

0.072

Sift

Benign

0.54

Sift4G

Benign

0.50

Polyphen

0.63

Vest4

0.19

MutPred

0.28

Gain of solvent accessibility (P = 0.0039)

MVP

0.23

MPC

1.5

ClinPred

0.30

GERP RS

2.0

PromoterAI

0.011

Neutral

(source)

Varity_R

0.099

gMVP

0.21

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over