rs17695092

chr5-173910850-T-G

Variant summary

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

The NM_030627.4(CPEB4):c.1207+246T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 429,050 control chromosomes in the GnomAD database, including 15,947 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 0.22 (4958 hom., cov: 31)
  • Exomes 𝑓: 0.26 (10989 hom.)
• Consequence: CPEB4 NM_030627.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPEB4	NM_030627.4	c.1207+246T>G		intron_variant		ENST00000265085.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPEB4	ENST00000265085.10	c.1207+246T>G		intron_variant		1	NM_030627.4

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33759 AN: 151964 Hom.: 4959 Cov.: 31

Gnomad AFR AF: 0.0669

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.0812

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.263 AC: 72823 AN: 276968 Hom.: 10989 Cov.: 0 AF XY: 0.257 AC XY: 37045 AN XY: 144250

Gnomad4 AFR exome AF: 0.0697

Gnomad4 AMR exome AF: 0.173

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.0879

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.409

Gnomad4 NFE exome AF: 0.297

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.222 AC: 33748 AN: 152082 Hom.: 4958 Cov.: 31 AF XY: 0.225 AC XY: 16729 AN XY: 74332

Gnomad4 AFR AF: 0.0667

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.0808

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.188

Alfa AF: 0.250 Hom.: 900

Bravo AF: 0.196

Asia WGS AF: 0.0880 AC: 306 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.68
Dann	Benign	0.63

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: rs17695092; hg19: chr5-173337853;