rs2287497

Positions:

• chr17-7689462-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001143992.2(WRAP53):​c.531-128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,246,102 control chromosomes in the GnomAD database, including 21,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (7725 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13397 hom.)
• Consequence: WRAP53 NM_001143992.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.439

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]

WRAP53 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-7689462-G-A is Benign according to our data. Variant chr17-7689462-G-A is described in ClinVar as [Benign]. Clinvar id is 1258203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WRAP53	NM_001143992.2	c.531-128G>A		intron_variant		ENST00000396463.7	NP_001137464.1
WRAP53	NM_001143990.2	c.531-128G>A		intron_variant			NP_001137462.1
WRAP53	NM_001143991.2	c.531-128G>A		intron_variant			NP_001137463.1
WRAP53	NM_018081.2	c.531-128G>A		intron_variant			NP_060551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WRAP53	ENST00000396463.7	c.531-128G>A		intron_variant		1	NM_001143992.2	ENSP00000379727.3

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37400 AN: 151778 Hom.: 7714 Cov.: 32

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0591

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.126 AC: 137724 AN: 1094204 Hom.: 13397 Cov.: 15 AF XY: 0.128 AC XY: 71484 AN XY: 556792

Gnomad4 AFR exome AF: 0.570

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.0930

Gnomad4 EAS exome AF: 0.282

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.0591

Gnomad4 NFE exome AF: 0.0949

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.247 AC: 37443 AN: 151898 Hom.: 7725 Cov.: 32 AF XY: 0.242 AC XY: 17960 AN XY: 74268

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.0968

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.0591

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.211

Alfa AF: 0.131 Hom.: 3034

Bravo AF: 0.269

Asia WGS AF: 0.275 AC: 955 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.5
DANN	Benign	0.67

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: rs2287497; hg19: chr17-7592780;