Genetic Variant NM_014912.5:c.1454-7658T>C (chr10-92118852-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014912.5(CPEB3):c.1454-7658T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 787,572 control chromosomes in the GnomAD database, including 48,073 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 0.40 ( 12712 hom., cov: 32)

Exomes 𝑓: 0.32 ( 35361 hom. )

Consequence

CPEB3
NM_014912.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.485

Publications

3 publications found

Variant links:

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 links:

SDHCP2 (HGNC:45177): (succinate dehydrogenase complex subunit C pseudogene 2)

SDHCP2 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPEB3	NM_014912.5	MANE Select	c.1454-7658T>C		intron	N/A	NP_055727.3
	CPEB3	NM_001178137.2		c.1412-7658T>C		intron	N/A	NP_001171608.1	Q5QP71

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CPEB3	ENST00000265997.5	TSL:1 MANE Select	c.1454-7658T>C	intron	N/A	ENSP00000265997.4	Q8NE35-1
CPEB3	ENST00000412050.8	TSL:1	c.1412-7658T>C	intron	N/A	ENSP00000398310.2	Q8NE35-2
CPEB3	ENST00000903868.1		c.1505-7658T>C	intron	N/A	ENSP00000573927.1

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

59923

AN:

150952

Hom.:

12698

Cov.:

show subpopulations

Gnomad AFR

AF:

0.547

Gnomad AMI

AF:

0.361

Gnomad AMR

AF:

0.419

Gnomad ASJ

AF:

0.423

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.139

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.368

Gnomad NFE

AF:

0.344

Gnomad OTH

AF:

0.419

GnomAD4 exome

AF:

0.322

AC:

205247

AN:

636498

Hom.:

35361

Cov.:

AF XY:

0.313

AC XY:

108215

AN XY:

345422

show subpopulations

African (AFR)

AF:

0.549

AC:

9695

AN:

17670

American (AMR)

AF:

0.409

AC:

17644

AN:

43168

Ashkenazi Jewish (ASJ)

AF:

0.410

AC:

8412

AN:

20538

East Asian (EAS)

AF:

0.262

AC:

9424

AN:

36002

South Asian (SAS)

AF:

0.147

AC:

10097

AN:

68908

European-Finnish (FIN)

AF:

0.261

AC:

13682

AN:

52366

Middle Eastern (MID)

AF:

0.389

AC:

1094

AN:

2814

European-Non Finnish (NFE)

AF:

0.342

AC:

123757

AN:

362016

Other (OTH)

AF:

0.347

AC:

11442

AN:

33016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

7815

15630

23445

31260

39075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1020

2040

3060

4080

5100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.397

AC:

59987

AN:

151074

Hom.:

12712

Cov.:

AF XY:

0.389

AC XY:

28708

AN XY:

73836

show subpopulations

African (AFR)

AF:

0.547

AC:

22669

AN:

41408

American (AMR)

AF:

0.419

AC:

6316

AN:

15078

Ashkenazi Jewish (ASJ)

AF:

0.423

AC:

1447

AN:

3422

East Asian (EAS)

AF:

0.304

AC:

1574

AN:

5170

South Asian (SAS)

AF:

0.138

AC:

658

AN:

4756

European-Finnish (FIN)

AF:

0.265

AC:

2780

AN:

10494

Middle Eastern (MID)

AF:

0.379

AC:

110

AN:

290

European-Non Finnish (NFE)

AF:

0.344

AC:

23229

AN:

67454

Other (OTH)

AF:

0.418

AC:

876

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1783

3566

5349

7132

8915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.374

Hom.:

1473

Bravo

AF:

0.422

Asia WGS

AF:

0.225

AC:

786

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.027

(source)

DANN

Benign

0.35

PhyloP100

-0.48

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over