5-173890221-C-G

Variant names:

• chr5-173890221-C-G
• NM_030627.4:c.488C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030627.4(CPEB4):​c.488C>G​(p.Ser163Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,818 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: 6.8e-7 (0 hom.)
• Consequence: CPEB4 NM_030627.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPEB4	NM_030627.4	c.488C>G	p.Ser163Trp	missense_variant	Exon 1 of 10	ENST00000265085.10	NP_085130.2
CPEB4	NM_001308189.2	c.488C>G	p.Ser163Trp	missense_variant	Exon 1 of 9		NP_001295118.1
CPEB4	NM_001308191.2	c.488C>G	p.Ser163Trp	missense_variant	Exon 1 of 8		NP_001295120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPEB4	ENST00000265085.10	c.488C>G	p.Ser163Trp	missense_variant	Exon 1 of 10	1	NM_030627.4	ENSP00000265085.5
CPEB4	ENST00000334035.9	c.488C>G	p.Ser163Trp	missense_variant	Exon 1 of 9	1		ENSP00000334533.5
CPEB4	ENST00000520867.5	c.488C>G	p.Ser163Trp	missense_variant	Exon 1 of 8	1		ENSP00000429092.1
CPEB4	ENST00000519835.5	c.488C>G	p.Ser163Trp	missense_variant	Exon 1 of 7	1		ENSP00000429048.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461818 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727220

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.488C>G (p.S163W) alteration is located in exon 1 (coding exon 1) of the CPEB4 gene. This alteration results from a C to G substitution at nucleotide position 488, causing the serine (S) at amino acid position 163 to be replaced by a tryptophan (W). 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	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T;.;.;T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.99	D;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.72	D;D;D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.6	L;.;L;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.020	N;N;N;N
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.015	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.66
MutPred		0.29		Loss of disorder (P = 2e-04);Loss of disorder (P = 2e-04);Loss of disorder (P = 2e-04);Loss of disorder (P = 2e-04);
MVP		0.73
MPC		1.5
ClinPred		0.90	D
GERP RS		5.8
Varity_R		0.42
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr5-173317224;