5-173890322-G-C

Position:

chr5-173890322-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030627.4(CPEB4):c.589G>C(p.Ala197Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 6.8e-7 ( 0 hom. )

Consequence

CPEB4
NM_030627.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.08

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08941582).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CPEB4	NM_030627.4 linkuse as main transcript	c.589G>C	p.Ala197Pro	missense_variant	1/10	ENST00000265085.10	NP_085130.2
CPEB4	NM_001308189.2 linkuse as main transcript	c.589G>C	p.Ala197Pro	missense_variant	1/9		NP_001295118.1
CPEB4	NM_001308191.2 linkuse as main transcript	c.589G>C	p.Ala197Pro	missense_variant	1/8		NP_001295120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPEB4	ENST00000265085.10 linkuse as main transcript	c.589G>C	p.Ala197Pro	missense_variant	1/10	1	NM_030627.4	ENSP00000265085		Q17RY0-1
CPEB4	ENST00000334035.9 linkuse as main transcript	c.589G>C	p.Ala197Pro	missense_variant	1/9	1		ENSP00000334533	A1	Q17RY0-2
CPEB4	ENST00000520867.5 linkuse as main transcript	c.589G>C	p.Ala197Pro	missense_variant	1/8	1		ENSP00000429092	P4
CPEB4	ENST00000519835.5 linkuse as main transcript	c.589G>C	p.Ala197Pro	missense_variant	1/7	1		ENSP00000429048

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152154

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:

0.000385

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

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251436

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727240

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:

0.0000131

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

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

Mar 19, 2024

The c.589G>C (p.A197P) alteration is located in exon 1 (coding exon 1) of the CPEB4 gene. This alteration results from a G to C substitution at nucleotide position 589, causing the alanine (A) at amino acid position 197 to be replaced by a proline (P). 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

0.10

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.016

T;.;.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.81

T;T;T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.089

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;N;.

MutationTaster

Benign

0.74

N;N;N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.36

N;N;N;N

REVEL

Benign

0.063

Sift

Benign

0.36

T;T;T;T

Sift4G

Benign

0.15

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.17

MutPred

0.24

Gain of catalytic residue at P196 (P = 0.0183);Gain of catalytic residue at P196 (P = 0.0183);Gain of catalytic residue at P196 (P = 0.0183);Gain of catalytic residue at P196 (P = 0.0183);

MVP

0.26

MPC

0.54

ClinPred

0.074

GERP RS

5.0

Varity_R

0.087

gMVP

0.46

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