Variant 5-173890755-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_030627.4(CPEB4):c.1022A>G(p.Asn341Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,614,070 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CPEB4
NM_030627.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.21

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, CPEB4

BP4

Computational evidence support a benign effect (MetaRNN=0.182677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CPEB4	NM_030627.4 linkuse as main transcript	c.1022A>G	p.Asn341Ser	missense_variant	1/10	ENST00000265085.10
CPEB4	NM_001308189.2 linkuse as main transcript	c.1022A>G	p.Asn341Ser	missense_variant	1/9
CPEB4	NM_001308191.2 linkuse as main transcript	c.1022A>G	p.Asn341Ser	missense_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPEB4	ENST00000265085.10 linkuse as main transcript	c.1022A>G	p.Asn341Ser	missense_variant	1/10	1	NM_030627.4		Q17RY0-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152176

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2023

The c.1022A>G (p.N341S) 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 1022, causing the asparagine (N) at amino acid position 341 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

0.063

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.066

T;.;.;T

Eigen

Benign

0.072

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.0081

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.0

M;.;M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.5

N;N;D;D

REVEL

Benign

0.13

Sift

Benign

0.034

D;D;D;D

Sift4G

Benign

0.26

T;T;T;T

Polyphen

0.022

B;B;B;B

Vest4

0.29

MutPred

0.28

Gain of ubiquitination at K336 (P = 0.0683);Gain of ubiquitination at K336 (P = 0.0683);Gain of ubiquitination at K336 (P = 0.0683);Gain of ubiquitination at K336 (P = 0.0683);

MVP

0.66

MPC

0.33

ClinPred

0.86

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.76

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