Variant 5-173890650-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_030627.4(CPEB4):c.917A>G(p.Tyr306Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 5.90

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

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.917A>G	p.Tyr306Cys	missense_variant	1/10	ENST00000265085.10	NP_085130.2
CPEB4	NM_001308189.2 linkuse as main transcript	c.917A>G	p.Tyr306Cys	missense_variant	1/9		NP_001295118.1
CPEB4	NM_001308191.2 linkuse as main transcript	c.917A>G	p.Tyr306Cys	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.917A>G	p.Tyr306Cys	missense_variant	1/10	1	NM_030627.4	ENSP00000265085		Q17RY0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 22, 2024

The c.917A>G (p.Y306C) 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 917, causing the tyrosine (Y) at amino acid position 306 to be replaced by a cysteine (C). 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

0.069

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

T;.;.;T

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.45

T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.5

L;.;L;.

MutationTaster

Benign

0.94

D;D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.2

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.12

T;T;T;T

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.99

D;D;D;D

Vest4

0.60

MutPred

0.21

Loss of MoRF binding (P = 0.0847);Loss of MoRF binding (P = 0.0847);Loss of MoRF binding (P = 0.0847);Loss of MoRF binding (P = 0.0847);

MVP

0.37

MPC

1.2

ClinPred

0.95

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.65

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over