rs701846

Positions:

• chr10-92111309-G-A
• chr10-92111309-G-C
• chr10-92111309-G-T

Variant summary

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

The NM_014912.5(CPEB3):​c.1454-115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 744,904 control chromosomes in the GnomAD database, including 141,741 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 0.68 (36746 hom., cov: 34)
  • Exomes 𝑓: 0.59 (104995 hom.)
• Consequence: CPEB3 NM_014912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

Genes affected

CPEB3 (HGNC:21746): (cytoplasmic polyadenylation element binding protein 3) Enables mRNA 3'-UTR binding activity and translation factor activity, RNA binding. Involved in cellular response to amino acid stimulus; negative regulation of transcription by RNA polymerase II; and positive regulation of mRNA catabolic process. Located in several cellular components, including cytosol; midbody; and nucleoplasm. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPEB3	NM_014912.5	c.1454-115C>T		intron_variant		ENST00000265997.5	NP_055727.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPEB3	ENST00000265997.5	c.1454-115C>T		intron_variant		1	NM_014912.5	ENSP00000265997.4
CPEB3	ENST00000412050.8	c.1412-115C>T		intron_variant		1		ENSP00000398310.2
CPEB3	ENST00000614585.4	c.1454-115C>T		intron_variant		5		ENSP00000482128.1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103337 AN: 152122 Hom.: 36709 Cov.: 34

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.708

GnomAD4 exome AF: 0.589 AC: 348794 AN: 592664 Hom.: 104995 AF XY: 0.581 AC XY: 184128 AN XY: 316896

Gnomad4 AFR exome AF: 0.889

Gnomad4 AMR exome AF: 0.708

Gnomad4 ASJ exome AF: 0.655

Gnomad4 EAS exome AF: 0.504

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.488

Gnomad4 NFE exome AF: 0.603

Gnomad4 OTH exome AF: 0.615

GnomAD4 genome AF: 0.679 AC: 103433 AN: 152240 Hom.: 36746 Cov.: 34 AF XY: 0.668 AC XY: 49734 AN XY: 74424

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.715

Gnomad4 ASJ AF: 0.672

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.709

Alfa AF: 0.619 Hom.: 14038

Bravo AF: 0.714

Asia WGS AF: 0.499 AC: 1739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.81
DANN	Benign	0.40

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: rs701846; hg19: chr10-93871066;