chr17-7688193-C-CG

Position:

• chr17-7688193-C-CG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000316024.9(WRAP53):​c.-449dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 182,602 control chromosomes in the GnomAD database, including 2,377 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (2222 hom., cov: 30)
  • Exomes 𝑓: 0.085 (155 hom.)
• Consequence: WRAP53 ENST00000316024.9 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.171

Genes affected

WRAP53 (HGNC:25522): (WD repeat containing antisense to TP53) This gene encodes an essential component of the telomerase holoenzyme complex, a ribonucleoprotein complex required for telomere synthesis. This protein is enriched in Cajal bodies, nuclear sites of RNP processing that are important for telomerase function. It interacts with dyskerin, TERT and TERC, other components of active telomerase, and with small Cajal body RNAs (scaRNAs), which are involved in modifying splicing RNAs. This mRNA also functions as a p53 antisense transcript, that regulates endogenous p53 mRNA levels and further induction of p53 protein by targeting the 5' untranslated region of p53 mRNA. Alternatively spliced transcript variants which differ only in the 5' UTR have been found for this gene. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-7688193-C-CG is Benign according to our data. Variant chr17-7688193-C-CG is described in ClinVar as [Benign]. Clinvar id is 1182360.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WRAP53	NM_001143990.2	c.-1-448dup		intron_variant
WRAP53	NM_001143991.2	c.-1-448dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WRAP53	ENST00000316024.9	c.-449dup		5_prime_UTR_variant	1/10	1		P1
WRAP53	ENST00000431639.6	c.-1-448dup		intron_variant		1		P1
WRAP53	ENST00000457584.6	c.-1-448dup		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21753 AN: 151834 Hom.: 2218 Cov.: 30

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.0454

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0714

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.0850 AC: 2606 AN: 30650 Hom.: 155 Cov.: 0 AF XY: 0.0929 AC XY: 1495 AN XY: 16088

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.0496

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.155

Gnomad4 FIN exome AF: 0.0347

Gnomad4 NFE exome AF: 0.0553

Gnomad4 OTH exome AF: 0.0726

GnomAD4 genome AF: 0.143 AC: 21788 AN: 151952 Hom.: 2222 Cov.: 30 AF XY: 0.143 AC XY: 10657 AN XY: 74272

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0804

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.0454

Gnomad4 NFE AF: 0.0714

Gnomad4 OTH AF: 0.126

Bravo AF: 0.153

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs17551157; hg19: chr17-7591511;