10-92184882-T-C

Variant names:

• chr10-92184882-T-C
• rs3781230
• NM_014912.5:c.1166-3863A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014912.5(CPEB3):​c.1166-3863A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,056 control chromosomes in the GnomAD database, including 10,746 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 0.35 (10746 hom., cov: 32)
• Consequence: CPEB3 NM_014912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 3 publications found

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]

CPEB3 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPEB3	NM_014912.5	c.1166-3863A>G		intron_variant	Intron 3 of 9	ENST00000265997.5	NP_055727.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPEB3	ENST00000265997.5	c.1166-3863A>G		intron_variant	Intron 3 of 9	1	NM_014912.5	ENSP00000265997.4
CPEB3	ENST00000412050.8	c.1097-3863A>G		intron_variant	Intron 3 of 9	1		ENSP00000398310.2
CPEB3	ENST00000614585.4	c.1166-3863A>G		intron_variant	Intron 3 of 9	5		ENSP00000482128.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53719 AN: 151938 Hom.: 10731 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.363

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.354 AC: 53779 AN: 152056 Hom.: 10746 Cov.: 32 AF XY: 0.344 AC XY: 25576 AN XY: 74332

African (AFR) AF: 0.529 AC: 21928 AN: 41474

American (AMR) AF: 0.277 AC: 4234 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1320 AN: 3472

East Asian (EAS) AF: 0.120 AC: 619 AN: 5178

South Asian (SAS) AF: 0.125 AC: 604 AN: 4832

European-Finnish (FIN) AF: 0.234 AC: 2472 AN: 10554

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21544 AN: 67954

Other (OTH) AF: 0.362 AC: 762 AN: 2104

Alfa AF: 0.342 Hom.: 1806

Bravo AF: 0.368

Asia WGS AF: 0.153 AC: 531 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.4
DANN	Benign	0.69
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3781230; hg19: chr10-93944639;