15-82557848-C-T

Variant names:

• chr15-82557848-C-T
• rs200353216
• NM_001365242.1:c.599G>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001365242.1(CPEB1):​c.599G>A​(p.Arg200Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000539 in 1,613,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (0 hom.)
• Consequence: CPEB1 NM_001365242.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.79

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.062473834).
• BS2: High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPEB1	NM_001365242.1	c.599G>A	p.Arg200Gln	missense_variant	Exon 5 of 13	ENST00000684509.1	NP_001352171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPEB1	ENST00000684509.1	c.599G>A	p.Arg200Gln	missense_variant	Exon 5 of 13		NM_001365242.1	ENSP00000507835.1
ENSG00000260836	ENST00000562833.2	c.293G>A	p.Arg98Gln	missense_variant	Exon 2 of 13	3		ENSP00000454786.2

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 152072 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000413 AC: 103 AN: 249504 Hom.: 0 AF XY: 0.000451 AC XY: 61 AN XY: 135356

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000417

Gnomad NFE exome AF: 0.000786

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000563 AC: 823 AN: 1461888 Hom.: 0 Cov.: 30 AF XY: 0.000573 AC XY: 417 AN XY: 727242

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000711

Gnomad4 NFE exome AF: 0.000658

Gnomad4 OTH exome AF: 0.000729

GnomAD4 genome AF: 0.000309 AC: 47 AN: 152072 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74284

Gnomad4 AFR AF: 0.0000725

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.000573

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000513 Hom.: 0

Bravo AF: 0.000321

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000481 AC: 4

ExAC AF: 0.000587 AC: 71

EpiCase AF: 0.000382

EpiControl AF: 0.000533

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.518G>A (p.R173Q) alteration is located in exon 4 (coding exon 4) of the CPEB1 gene. This alteration results from a G to A substitution at nucleotide position 518, causing the arginine (R) at amino acid position 173 to be replaced by a glutamine (Q). 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	-0.47	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	.;T;.;.;.;.;.;.;.;.;.;.
Eigen	Benign	-0.19
Eigen_PC	Benign	0.029
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D;.;.;.;D;.;.;.;.;.;.
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.062	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	.;.;.;.;.;L;.;.;.;.;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.53	.;.;.;.;.;.;.;.;.;.;.;N
Sift	Benign	0.35	.;.;.;.;.;.;.;.;.;.;.;T
Sift4G	Benign	0.27	.;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.017	.;.;.;.;.;B;.;.;.;.;.;.
Vest4		0.11, 0.11, 0.13, 0.13, 0.12, 0.15, 0.15, 0.16
MVP		0.37
ClinPred		0.031	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.30

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

Other links and lift over

dbSNP: rs200353216; hg19: chr15-83226598;