rs969518

Variant names:

• chr5-173953343-C-T
• rs969518
• ENST00000519835.5:c.*38C>T

Variant summary

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

The ENST00000519835.5(CPEB4):​c.*38C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 1,209,040 control chromosomes in the GnomAD database, including 186,197 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 0.54 (22328 hom., cov: 32)
  • Exomes 𝑓: 0.55 (163869 hom.)
• Consequence: CPEB4 ENST00000519835.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

Genes affected

CPEB4 (HGNC:21747): (cytoplasmic polyadenylation element binding protein 4) Enables RNA binding activity. Predicted to be involved in several processes, including cellular response to glucose starvation; negative regulation of cytoplasmic translation; and response to ischemia. Located in cytoplasm and nucleus. Biomarker of liver cirrhosis; portal hypertension; and primary biliary cholangitis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPEB4	NM_030627.4	c.1962+71C>T		intron_variant	Intron 9 of 9	ENST00000265085.10	NP_085130.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPEB4	ENST00000265085.10	c.1962+71C>T		intron_variant	Intron 9 of 9	1	NM_030627.4	ENSP00000265085.5

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81442 AN: 151896 Hom.: 22325 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.509

GnomAD3 exomes AF: 0.533 AC: 86750 AN: 162802 Hom.: 23837 AF XY: 0.541 AC XY: 46697 AN XY: 86394

Gnomad AFR exome AF: 0.507

Gnomad AMR exome AF: 0.359

Gnomad ASJ exome AF: 0.516

Gnomad EAS exome AF: 0.323

Gnomad SAS exome AF: 0.592

Gnomad FIN exome AF: 0.661

Gnomad NFE exome AF: 0.578

Gnomad OTH exome AF: 0.541

GnomAD4 exome AF: 0.552 AC: 583926 AN: 1057026 Hom.: 163869 Cov.: 13 AF XY: 0.554 AC XY: 288571 AN XY: 521326

Gnomad4 AFR exome AF: 0.508

Gnomad4 AMR exome AF: 0.372

Gnomad4 ASJ exome AF: 0.532

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.598

Gnomad4 FIN exome AF: 0.649

Gnomad4 NFE exome AF: 0.564

Gnomad4 OTH exome AF: 0.537

GnomAD4 genome AF: 0.536 AC: 81468 AN: 152014 Hom.: 22328 Cov.: 32 AF XY: 0.538 AC XY: 39973 AN XY: 74316

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.508

Alfa AF: 0.576 Hom.: 32820

Bravo AF: 0.508

Asia WGS AF: 0.467 AC: 1627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.2
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs969518; hg19: chr5-173380346; COSMIC: COSV54171680;