Genetic Variant CEBPB:p.Asp272Tyr (chr20-50191847-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005194.4(CEBPB):c.814G>T(p.Asp272Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,454,096 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D272N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CEBPB
NM_005194.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.69

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.814G>T	p.Asp272Tyr	missense	Exon 1 of 1	NP_005185.2
CEBPB	NM_001285878.1		c.745G>T	p.Asp249Tyr	missense	Exon 1 of 1	NP_001272807.1	P17676-2
CEBPB	NM_001285879.1		c.220G>T	p.Asp74Tyr	missense	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.814G>T	p.Asp272Tyr	missense	Exon 1 of 1	ENSP00000305422.3	P17676-1
CEBPB	ENST00000718336.1		c.814G>T	p.Asp272Tyr	missense	Exon 1 of 1	ENSP00000520773.1	P17676-1
CEBPB-AS1	ENST00000751366.1		n.118+75C>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454096

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722862

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33192

American (AMR)

AF:

0.00

AC:

AN:

43822

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25950

East Asian (EAS)

AF:

0.00

AC:

AN:

39224

South Asian (SAS)

AF:

0.00

AC:

AN:

85004

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108758

Other (OTH)

AF:

0.00

AC:

AN:

60068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.75

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.94

M_CAP

Pathogenic

0.90

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.1

PhyloP100

3.7

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-4.2

REVEL

Uncertain

0.31

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.45

MutPred

0.42

Loss of ubiquitination at K275 (P = 0.02)

MVP

0.64

MPC

2.9

ClinPred

1.0

GERP RS

3.2

Varity_R

0.80

gMVP

0.90

Mutation Taster

=31/69

disease causing

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over