Genetic Variant NM_005194.4:c.578C>A (chr20-50191611-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

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. 14/22 in silico tools predict a benign outcome for this variant. 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. P193A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000092 ( 0 hom. )

Consequence

CEBPB
NM_005194.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.379

Publications

1 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22636735).

BS2

High AC in GnomAdExome4 at 11 AD gene.

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.578C>A	p.Pro193Gln	missense	Exon 1 of 1	NP_005185.2
CEBPB	NM_001285878.1		c.509C>A	p.Pro170Gln	missense	Exon 1 of 1	NP_001272807.1	P17676-2
CEBPB	NM_001285879.1		c.-17C>A		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.578C>A	p.Pro193Gln	missense	Exon 1 of 1	ENSP00000305422.3	P17676-1
CEBPB	ENST00000718336.1		c.578C>A	p.Pro193Gln	missense	Exon 1 of 1	ENSP00000520773.1	P17676-1
CEBPB-AS1	ENST00000751366.1		n.118+311G>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.000104

AC:

AN:

19196

AF XY:

0.0000796

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000922

AC:

AN:

1193102

Hom.:

Cov.:

AF XY:

0.0000120

AC XY:

AN XY:

581240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23196

American (AMR)

AF:

0.00

AC:

AN:

9380

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17278

East Asian (EAS)

AF:

0.00

AC:

AN:

26518

South Asian (SAS)

AF:

0.00

AC:

AN:

45680

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29722

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3356

European-Non Finnish (NFE)

AF:

0.0000111

AC:

AN:

989398

Other (OTH)

AF:

0.00

AC:

AN:

48574

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.19

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.55

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.38

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.1

REVEL

Benign

0.087

Sift

Benign

0.23

Sift4G

Benign

0.44

Polyphen

0.94

Vest4

0.16

MutPred

0.22

Gain of solvent accessibility (P = 0.1505)

MVP

0.73

MPC

1.3

ClinPred

0.31

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.12

gMVP

0.25

Mutation Taster

=92/8

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over