rs7086446

Variant names:

• chr10-92118852-A-G
• rs7086446
• NM_014912.5:c.1454-7658T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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]

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

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 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

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

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

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

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
DANN	Benign	0.35
PhyloP100		-0.48
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: rs7086446; hg19: chr10-93878609; COSMIC: COSV56455903;