rs17763373

Positions:

• chr5-173932328-A-G

Variant summary

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

The NM_030627.4(CPEB4):​c.1208-122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 626,444 control chromosomes in the GnomAD database, including 969 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 0.042 (185 hom., cov: 33)
  • Exomes 𝑓: 0.051 (784 hom.)
• Consequence: CPEB4 NM_030627.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPEB4	NM_030627.4	c.1208-122A>G		intron_variant		ENST00000265085.10	NP_085130.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPEB4	ENST00000265085.10	c.1208-122A>G		intron_variant		1	NM_030627.4	ENSP00000265085.5

Frequencies

GnomAD3 genomes AF: 0.0424 AC: 6448 AN: 152172 Hom.: 185 Cov.: 33

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0476

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00620

Gnomad FIN AF: 0.0400

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0634

Gnomad OTH AF: 0.0526

GnomAD4 exome AF: 0.0514 AC: 24391 AN: 474154 Hom.: 784 AF XY: 0.0501 AC XY: 12654 AN XY: 252444

Gnomad4 AFR exome AF: 0.0110

Gnomad4 AMR exome AF: 0.0396

Gnomad4 ASJ exome AF: 0.0655

Gnomad4 EAS exome AF: 0.000104

Gnomad4 SAS exome AF: 0.00820

Gnomad4 FIN exome AF: 0.0421

Gnomad4 NFE exome AF: 0.0651

Gnomad4 OTH exome AF: 0.0498

GnomAD4 genome AF: 0.0423 AC: 6448 AN: 152290 Hom.: 185 Cov.: 33 AF XY: 0.0411 AC XY: 3057 AN XY: 74466

Gnomad4 AFR AF: 0.0111

Gnomad4 AMR AF: 0.0475

Gnomad4 ASJ AF: 0.0706

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00662

Gnomad4 FIN AF: 0.0400

Gnomad4 NFE AF: 0.0634

Gnomad4 OTH AF: 0.0521

Alfa AF: 0.0582 Hom.: 488

Bravo AF: 0.0418

Asia WGS AF: 0.00376 AC: 14 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.0
DANN	Benign	0.76

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: rs17763373; hg19: chr5-173359331;