dbSNP rs756721024: CPEB4:p.Ser123Pro (chr5-173890100-T-C) – 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_030627.4(CPEB4):c.367T>C(p.Ser123Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000366 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

CPEB4
NM_030627.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.92

Publications

0 publications found

Variant links:

Genes affected

CPEB4 (HGNC:21747): (cytoplasmic polyadenylation element binding protein 4) Enables RNA binding activity. Predicted to be involved in several processes, including cellular response to glucose starvation; negative regulation of cytoplasmic translation; and response to ischemia. Located in cytoplasm and nucleus. Biomarker of liver cirrhosis; portal hypertension; and primary biliary cholangitis. [provided by Alliance of Genome Resources, Apr 2022]

CPEB4 links:

Genome browser will be placed here

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=0.16220969).

BS2

High AC in GnomAdExome4 at 57 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030627.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPEB4	NM_030627.4	MANE Select	c.367T>C	p.Ser123Pro	missense	Exon 1 of 10	NP_085130.2	Q17RY0-1
CPEB4	NM_001308189.2		c.367T>C	p.Ser123Pro	missense	Exon 1 of 9	NP_001295118.1	Q17RY0-2
CPEB4	NM_001308191.2		c.367T>C	p.Ser123Pro	missense	Exon 1 of 8	NP_001295120.1	B7ZLQ8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPEB4	ENST00000265085.10	TSL:1 MANE Select	c.367T>C	p.Ser123Pro	missense	Exon 1 of 10	ENSP00000265085.5	Q17RY0-1
CPEB4	ENST00000334035.9	TSL:1	c.367T>C	p.Ser123Pro	missense	Exon 1 of 9	ENSP00000334533.5	Q17RY0-2
CPEB4	ENST00000520867.5	TSL:1	c.367T>C	p.Ser123Pro	missense	Exon 1 of 8	ENSP00000429092.1	B7ZLQ8

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251320

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.000123

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000390

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000459

AC:

AN:

1112006

Other (OTH)

AF:

0.0000662

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.0000131

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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:

0.0000386

Hom.:

Bravo

AF:

0.0000151

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

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

0.092

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0090

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

3.9

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.49

REVEL

Benign

0.17

Sift

Uncertain

0.0080

Sift4G

Benign

0.29

Polyphen

0.47

Vest4

0.27

MVP

0.42

MPC

0.62

ClinPred

0.22

GERP RS

6.0

Varity_R

0.36

gMVP

0.37

Mutation Taster

=63/37

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