15-82553478-C-T

Variant names:

• chr15-82553478-C-T
• rs2036631685
• NM_001365242.1:c.1133G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365242.1(CPEB1):​c.1133G>A​(p.Cys378Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 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: 6.8e-7 (0 hom.)
• Consequence: CPEB1 NM_001365242.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17

Genes affected

CPEB1 (HGNC:21744): (cytoplasmic polyadenylation element binding protein 1) This gene encodes a member of the cytoplasmic polyadenylation element binding protein family. This highly conserved protein binds to a specific RNA sequence, called the cytoplasmic polyadenylation element, found in the 3' untranslated region of some mRNAs. The encoded protein functions in both the cytoplasm and the nucleus. It is involved in the regulation of mRNA translation, as well as processing of the 3' untranslated region, and may play a role in cell proliferation and tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ENSG00000260836 (HGNC:):

ACMG classification

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=0.19253021).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPEB1	NM_001365242.1	c.1133G>A	p.Cys378Tyr	missense_variant	Exon 8 of 13	ENST00000684509.1	NP_001352171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPEB1	ENST00000684509.1	c.1133G>A	p.Cys378Tyr	missense_variant	Exon 8 of 13		NM_001365242.1	ENSP00000507835.1
ENSG00000260836	ENST00000562833.2	c.827G>A	p.Cys276Tyr	missense_variant	Exon 5 of 13	3		ENSP00000454786.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461420 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727028

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1052G>A (p.C351Y) alteration is located in exon 7 (coding exon 7) of the CPEB1 gene. This alteration results from a G to A substitution at nucleotide position 1052, causing the cysteine (C) at amino acid position 351 to be replaced by a tyrosine (Y). 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
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.024	.;T;.;.;.;.;.;.;.;.;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.056
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.94	D;D;.;.;.;D;.;.;.;.;.
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.2	.;.;.;.;.;L;.;.;.;.;.
PrimateAI	Pathogenic	0.91	D
Sift4G	Benign	1.0	.;T;T;T;T;T;T;T;T;T;T
Polyphen		0.12	.;.;.;.;.;B;.;.;.;.;.
Vest4		0.43, 0.42, 0.42, 0.40, 0.43, 0.40, 0.40, 0.40
MutPred		0.21		.;.;Gain of ubiquitination at K347 (P = 0.1079);.;.;Gain of ubiquitination at K347 (P = 0.1079);.;.;.;.;.;
MVP		0.24
ClinPred		0.74	D
GERP RS		3.6
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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

Other links and lift over

dbSNP: rs2036631685; hg19: chr15-83222228;