Genetic Variant CEBPD:p.Ala173Val (chr8-47737603-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005195.4(CEBPD):c.518C>T(p.Ala173Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 1,452,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

CEBPD
NM_005195.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

Publications

1 publications found

Variant links:

Genes affected

CEBPD (HGNC:1835): (CCAAT enhancer binding protein delta) The protein encoded by this intronless gene is a bZIP transcription factor which can bind as a homodimer to certain DNA regulatory regions. It can also form heterodimers with the related protein CEBP-alpha. The encoded protein is important in the regulation of genes involved in immune and inflammatory responses, and may be involved in the regulation of genes associated with activation and/or differentiation of macrophages. The cytogenetic location of this locus has been reported as both 8p11 and 8q11. [provided by RefSeq, Sep 2010]

CEBPD links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.060773104).

BS2

High AC in GnomAd4 at 40 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005195.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPD	NM_005195.4	MANE Select	c.518C>T	p.Ala173Val	missense	Exon 1 of 1	NP_005186.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPD	ENST00000408965.4	TSL:6 MANE Select	c.518C>T	p.Ala173Val	missense	Exon 1 of 1	ENSP00000386165.3	P49716

Frequencies

GnomAD3 genomes

AF:

0.000264

AC:

AN:

151672

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00145

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000201

AC:

AN:

49796

AF XY:

0.000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000184

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000466

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000206

AC:

268

AN:

1300402

Hom.:

Cov.:

AF XY:

0.000203

AC XY:

129

AN XY:

636950

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25860

American (AMR)

AF:

0.000128

AC:

AN:

23504

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19750

East Asian (EAS)

AF:

0.00

AC:

AN:

29626

South Asian (SAS)

AF:

0.00

AC:

AN:

64844

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39140

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3718

European-Non Finnish (NFE)

AF:

0.000239

AC:

249

AN:

1040150

Other (OTH)

AF:

0.000297

AC:

AN:

53810

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

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

AF:

0.000264

AC:

AN:

151780

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74196

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41492

American (AMR)

AF:

0.00144

AC:

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

67874

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000693

Hom.:

Bravo

AF:

0.000208

ExAC

AF:

0.000136

AC:

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

0.083

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.51

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.061

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

1.5

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.9

REVEL

Benign

0.054

Sift

Benign

0.049

Sift4G

Benign

0.070

Polyphen

0.14

Vest4

0.023

MutPred

0.14

Gain of MoRF binding (P = 0.0809)

MVP

0.31

ClinPred

0.052

GERP RS

2.4

Varity_R

0.094

gMVP

0.29

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over