NM_014912.5:c.1454-115C>G

Variant names:

• chr10-92111309-G-C
• rs701846
• NM_014912.5:c.1454-115C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014912.5(CPEB3):​c.1454-115C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000168 in 593,594 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: CPEB3 NM_014912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 9 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.1454-115C>G		intron	N/A	NP_055727.3
	CPEB3	NM_001178137.2		c.1412-115C>G		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.1454-115C>G		intron	N/A	ENSP00000265997.4
	CPEB3	ENST00000412050.8	TSL:1	c.1412-115C>G		intron	N/A	ENSP00000398310.2
	CPEB3	ENST00000614585.4	TSL:5	c.1454-115C>G		intron	N/A	ENSP00000482128.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000168 AC: 1 AN: 593594 Hom.: 0 AF XY: 0.00000315 AC XY: 1 AN XY: 317400

African (AFR) AF: 0.00 AC: 0 AN: 16050

American (AMR) AF: 0.00 AC: 0 AN: 34556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17608

East Asian (EAS) AF: 0.00 AC: 0 AN: 35536

South Asian (SAS) AF: 0.00 AC: 0 AN: 58852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47844

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2270

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 349660

Other (OTH) AF: 0.0000320 AC: 1 AN: 31218

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.62
DANN	Benign	0.63
PhyloP100		-1.6

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: rs701846; hg19: chr10-93871066;