rs2303846

Positions:

• chr15-82544529-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365242.1(CPEB1):​c.*63C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0932 in 1,267,352 control chromosomes in the GnomAD database, including 7,247 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1884 hom., cov: 32)
  • Exomes 𝑓: 0.088 (5363 hom.)
• Consequence: CPEB1 NM_001365242.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPEB1	NM_001365242.1	c.*63C>T		3_prime_UTR_variant	13/13	ENST00000684509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPEB1	ENST00000684509.1	c.*63C>T		3_prime_UTR_variant	13/13		NM_001365242.1
	ENST00000621893.1	n.110+3550G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20544 AN: 152134 Hom.: 1882 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0927

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.0625

Gnomad FIN AF: 0.0654

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0753

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.0875 AC: 97591 AN: 1115100 Hom.: 5363 Cov.: 14 AF XY: 0.0853 AC XY: 48029 AN XY: 563094

Gnomad4 AFR exome AF: 0.240

Gnomad4 AMR exome AF: 0.182

Gnomad4 ASJ exome AF: 0.0821

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.0615

Gnomad4 FIN exome AF: 0.0664

Gnomad4 NFE exome AF: 0.0755

Gnomad4 OTH exome AF: 0.0979

GnomAD4 genome AF: 0.135 AC: 20570 AN: 152252 Hom.: 1884 Cov.: 32 AF XY: 0.135 AC XY: 10060 AN XY: 74442

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.0927

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.0622

Gnomad4 FIN AF: 0.0654

Gnomad4 NFE AF: 0.0754

Gnomad4 OTH AF: 0.130

Alfa AF: 0.115 Hom.: 116

Bravo AF: 0.146

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	10
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2303846; hg19: chr15-83213279;