rs7086446

chr10-92118852-A-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485

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]

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

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPEB3	NM_014912.5	c.1454-7658T>C		intron_variant		ENST00000265997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPEB3	ENST00000265997.5	c.1454-7658T>C		intron_variant		1	NM_014912.5
CPEB3	ENST00000412050.8	c.1412-7658T>C		intron_variant		1		P1
SDHCP2	ENST00000398565.2	n.189A>G		non_coding_transcript_exon_variant	1/1
CPEB3	ENST00000614585.4	c.1454-7658T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.397 AC: 59923 AN: 150952 Hom.: 12698 Cov.: 32

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.: 6 AF XY: 0.313 AC XY: 108215 AN XY: 345422

Gnomad4 AFR exome AF: 0.549

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.410

Gnomad4 EAS exome AF: 0.262

Gnomad4 SAS exome AF: 0.147

Gnomad4 FIN exome AF: 0.261

Gnomad4 NFE exome AF: 0.342

Gnomad4 OTH exome AF: 0.347

GnomAD4 genome AF: 0.397 AC: 59987 AN: 151074 Hom.: 12712 Cov.: 32 AF XY: 0.389 AC XY: 28708 AN XY: 73836

Gnomad4 AFR AF: 0.547

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.418

Alfa AF: 0.367 Hom.: 1358

Bravo AF: 0.422

Asia WGS AF: 0.225 AC: 786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.027
Dann	Benign	0.35

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: rs7086446; hg19: chr10-93878609; COSMIC: COSV56455903;