Genetic Variant CPEB4:p.Asn52Ser (chr5-173889888-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_030627.4(CPEB4):c.155A>G(p.Asn52Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

CPEB4
NM_030627.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.94

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09435961).

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPEB4	NM_030627.4 link	c.155A>G	p.Asn52Ser	missense_variant	Exon 1 of 10	ENST00000265085.10	NP_085130.2	Q17RY0-1
CPEB4	NM_001308189.2 link	c.155A>G	p.Asn52Ser	missense_variant	Exon 1 of 9		NP_001295118.1	Q17RY0-2
CPEB4	NM_001308191.2 link	c.155A>G	p.Asn52Ser	missense_variant	Exon 1 of 8		NP_001295120.1	Q17RY0B7ZLQ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CPEB4	ENST00000265085.10 link	c.155A>G	p.Asn52Ser	missense_variant	Exon 1 of 10	1	NM_030627.4	ENSP00000265085.5	Q17RY0-1
CPEB4	ENST00000334035.9 link	c.155A>G	p.Asn52Ser	missense_variant	Exon 1 of 9	1		ENSP00000334533.5	Q17RY0-2
CPEB4	ENST00000520867.5 link	c.155A>G	p.Asn52Ser	missense_variant	Exon 1 of 8	1		ENSP00000429092.1	B7ZLQ8
CPEB4	ENST00000519835.5 link	c.155A>G	p.Asn52Ser	missense_variant	Exon 1 of 7	1		ENSP00000429048.1	E5RJM0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250840

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135846

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 SAS 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:

0.00000821

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.155A>G (p.N52S) alteration is located in exon 1 (coding exon 1) of the CPEB4 gene. This alteration results from a A to G substitution at nucleotide position 155, causing the asparagine (N) at amino acid position 52 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.020

T;.;.;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.094

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.;L;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.46

N;N;N;N

REVEL

Benign

0.080

Sift

Benign

0.25

T;T;T;T

Sift4G

Benign

0.69

T;T;T;T

Polyphen

0.010

B;B;B;B

Vest4

0.14

MutPred

0.31

Gain of glycosylation at N52 (P = 0.002);Gain of glycosylation at N52 (P = 0.002);Gain of glycosylation at N52 (P = 0.002);Gain of glycosylation at N52 (P = 0.002);

MVP

0.53

MPC

0.34

ClinPred

0.63

GERP RS

3.3

Varity_R

0.11

gMVP

0.44

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over