Variant 5-173889849-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_030627.4(CPEB4):c.116C>A(p.Pro39His) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,894 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: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CPEB4
NM_030627.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86

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=0.18979013).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CPEB4	NM_030627.4 linkuse as main transcript	c.116C>A	p.Pro39His	missense_variant	1/10	ENST00000265085.10	NP_085130.2
CPEB4	NM_001308189.2 linkuse as main transcript	c.116C>A	p.Pro39His	missense_variant	1/9		NP_001295118.1
CPEB4	NM_001308191.2 linkuse as main transcript	c.116C>A	p.Pro39His	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.116C>A	p.Pro39His	missense_variant	1/10	1	NM_030627.4	ENSP00000265085		Q17RY0-1
CPEB4	ENST00000334035.9 linkuse as main transcript	c.116C>A	p.Pro39His	missense_variant	1/9	1		ENSP00000334533	A1	Q17RY0-2
CPEB4	ENST00000520867.5 linkuse as main transcript	c.116C>A	p.Pro39His	missense_variant	1/8	1		ENSP00000429092	P4
CPEB4	ENST00000519835.5 linkuse as main transcript	c.116C>A	p.Pro39His	missense_variant	1/7	1		ENSP00000429048

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251226

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

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:

0.00000410

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000275

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:

0.000151

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

Cov.:

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

Jul 17, 2023

The c.116C>A (p.P39H) alteration is located in exon 1 (coding exon 1) of the CPEB4 gene. This alteration results from a C to A substitution at nucleotide position 116, causing the proline (P) at amino acid position 39 to be replaced by a histidine (H). 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

0.097

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.032

T;.;.;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.97

D;D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.19

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;.;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.99

N;N;N;N

REVEL

Benign

0.18

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Benign

0.41

T;T;T;T

Polyphen

0.74

P;P;P;P

Vest4

0.33

MutPred

0.15

Loss of glycosylation at P39 (P = 0.0385);Loss of glycosylation at P39 (P = 0.0385);Loss of glycosylation at P39 (P = 0.0385);Loss of glycosylation at P39 (P = 0.0385);

MVP

0.26

MPC

1.1

ClinPred

0.56

GERP RS

5.6

Varity_R

0.32

gMVP

0.32

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