5-173890377-G-A

Variant summary

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

The NM_030627.4(CPEB4):c.644G>A(p.Ser215Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,884 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CPEB4
NM_030627.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.14

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=0.24897525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CPEB4	NM_030627.4 linkuse as main transcript	c.644G>A	p.Ser215Asn	missense_variant	1/10	ENST00000265085.10
CPEB4	NM_001308189.2 linkuse as main transcript	c.644G>A	p.Ser215Asn	missense_variant	1/9
CPEB4	NM_001308191.2 linkuse as main transcript	c.644G>A	p.Ser215Asn	missense_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPEB4	ENST00000265085.10 linkuse as main transcript	c.644G>A	p.Ser215Asn	missense_variant	1/10	1	NM_030627.4		Q17RY0-1
CPEB4	ENST00000334035.9 linkuse as main transcript	c.644G>A	p.Ser215Asn	missense_variant	1/9	1		A1	Q17RY0-2
CPEB4	ENST00000520867.5 linkuse as main transcript	c.644G>A	p.Ser215Asn	missense_variant	1/8	1		P4
CPEB4	ENST00000519835.5 linkuse as main transcript	c.644G>A	p.Ser215Asn	missense_variant	1/7	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251426

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135888

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:

0.00000137

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727238

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Dec 01, 2023

The c.644G>A (p.S215N) alteration is located in exon 1 (coding exon 1) of the CPEB4 gene. This alteration results from a G to A substitution at nucleotide position 644, causing the serine (S) at amino acid position 215 to be replaced by an asparagine (N). 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

0.16

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.39

Cadd

Benign

Dann

Benign

0.93

DEOGEN2

Benign

0.013

T;.;.;T

Eigen

Benign

-0.11

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

N;.;N;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.76

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.74

T;T;T;T

Sift4G

Benign

0.48

T;T;T;T

Polyphen

0.0030

B;B;B;B

Vest4

0.63

MutPred

0.18

Loss of glycosylation at S215 (P = 0.1264);Loss of glycosylation at S215 (P = 0.1264);Loss of glycosylation at S215 (P = 0.1264);Loss of glycosylation at S215 (P = 0.1264);

MVP

0.49

MPC

0.39

ClinPred

0.29

GERP RS

5.6

Varity_R

0.23

gMVP

0.41

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