NM_014912.5:c.1869+8476C>T

Variant names:

• chr10-92072844-G-A
• rs1935864
• NM_014912.5:c.1869+8476C>T

Variant summary

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

The NM_014912.5(CPEB3):​c.1869+8476C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,054 control chromosomes in the GnomAD database, including 1,825 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 (1825 hom., cov: 32)
• Consequence: CPEB3 NM_014912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014912.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPEB3	NM_014912.5	MANE Select	c.1869+8476C>T		intron	N/A	NP_055727.3
	CPEB3	NM_001178137.2		c.1827+8476C>T		intron	N/A	NP_001171608.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPEB3	ENST00000265997.5	TSL:1 MANE Select	c.1869+8476C>T		intron	N/A	ENSP00000265997.4
	CPEB3	ENST00000412050.8	TSL:1	c.1827+8476C>T		intron	N/A	ENSP00000398310.2
	CPEB3	ENST00000614585.4	TSL:5	c.1869+8476C>T		intron	N/A	ENSP00000482128.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21441 AN: 151936 Hom.: 1816 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0878

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0985

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.141 AC: 21483 AN: 152054 Hom.: 1825 Cov.: 32 AF XY: 0.142 AC XY: 10523 AN XY: 74330

African (AFR) AF: 0.218 AC: 9023 AN: 41450

American (AMR) AF: 0.155 AC: 2374 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3470

East Asian (EAS) AF: 0.210 AC: 1085 AN: 5170

South Asian (SAS) AF: 0.170 AC: 818 AN: 4814

European-Finnish (FIN) AF: 0.0878 AC: 929 AN: 10578

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0985 AC: 6697 AN: 67996

Other (OTH) AF: 0.130 AC: 274 AN: 2102

Alfa AF: 0.0976 Hom.: 570

Bravo AF: 0.147

Asia WGS AF: 0.192 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		-0.15
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: rs1935864; hg19: chr10-93832601;