rs969518

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000519835.5. 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
	CPEB4	NM_030627.4	MANE Select	c.1962+71C>T		intron	N/A	NP_085130.2	Q17RY0-1
	CPEB4	NM_001308189.2		c.1911+71C>T		intron	N/A	NP_001295118.1	Q17RY0-2
	CPEB4	NM_001308191.2		c.1887+71C>T		intron	N/A	NP_001295120.1	B7ZLQ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPEB4	ENST00000519835.5	TSL:1	c.*38C>T		3_prime_UTR	Exon 7 of 7	ENSP00000429048.1	E5RJM0
	CPEB4	ENST00000265085.10	TSL:1 MANE Select	c.1962+71C>T		intron	N/A	ENSP00000265085.5	Q17RY0-1
	CPEB4	ENST00000334035.9	TSL:1	c.1911+71C>T		intron	N/A	ENSP00000334533.5	Q17RY0-2

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

GnomAD2 exomes AF: 0.533 AC: 86750 AN: 162802 AF XY: 0.541

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 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

African (AFR) AF: 0.508 AC: 12607 AN: 24802

American (AMR) AF: 0.372 AC: 9649 AN: 25942

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 8916 AN: 16758

East Asian (EAS) AF: 0.300 AC: 10974 AN: 36610

South Asian (SAS) AF: 0.598 AC: 28110 AN: 46968

European-Finnish (FIN) AF: 0.649 AC: 29959 AN: 46190

Middle Eastern (MID) AF: 0.563 AC: 2551 AN: 4530

European-Non Finnish (NFE) AF: 0.564 AC: 457060 AN: 810366

Other (OTH) AF: 0.537 AC: 24100 AN: 44860

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

African (AFR) AF: 0.505 AC: 20921 AN: 41412

American (AMR) AF: 0.421 AC: 6435 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1906 AN: 3468

East Asian (EAS) AF: 0.328 AC: 1695 AN: 5174

South Asian (SAS) AF: 0.586 AC: 2826 AN: 4820

European-Finnish (FIN) AF: 0.673 AC: 7112 AN: 10562

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38766 AN: 67986

Other (OTH) AF: 0.508 AC: 1072 AN: 2112

Alfa AF: 0.565 Hom.: 52067

Bravo AF: 0.508

Asia WGS AF: 0.467 AC: 1627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.2
DANN	Benign	0.51
PhyloP100		0.0010
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs969518;

hg19: chr5-173380346;

COSMIC: COSV54171680;