17-7689164-C-T

Position:

• chr17-7689164-C-T

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.432-60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 1,613,240 control chromosomes in the GnomAD database, including 4,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (401 hom., cov: 31)
  • Exomes 𝑓: 0.071 (4413 hom.)
• Consequence: WRAP53 NM_001143992.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.293

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=-0.82).
• BP6: Variant 17-7689164-C-T is Benign according to our data. Variant chr17-7689164-C-T is described in ClinVar as [Benign]. Clinvar id is 1275261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WRAP53	NM_001143992.2	c.432-60C>T		intron_variant		ENST00000396463.7	NP_001137464.1
WRAP53	NM_001143990.2	c.432-60C>T		intron_variant			NP_001137462.1
WRAP53	NM_001143991.2	c.432-60C>T		intron_variant			NP_001137463.1
WRAP53	NM_018081.2	c.432-60C>T		intron_variant			NP_060551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WRAP53	ENST00000396463.7	c.432-60C>T		intron_variant		1	NM_001143992.2	ENSP00000379727.3

Frequencies

GnomAD3 genomes AF: 0.0623 AC: 9457 AN: 151830 Hom.: 396 Cov.: 31

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0470

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.0849

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0612

Gnomad OTH AF: 0.0473

GnomAD4 exome AF: 0.0710 AC: 103761 AN: 1461292 Hom.: 4413 Cov.: 32 AF XY: 0.0738 AC XY: 53639 AN XY: 726946

Gnomad4 AFR exome AF: 0.0390

Gnomad4 AMR exome AF: 0.0559

Gnomad4 ASJ exome AF: 0.0575

Gnomad4 EAS exome AF: 0.0749

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.0637

Gnomad4 OTH exome AF: 0.0686

GnomAD4 genome AF: 0.0624 AC: 9485 AN: 151948 Hom.: 401 Cov.: 31 AF XY: 0.0668 AC XY: 4958 AN XY: 74228

Gnomad4 AFR AF: 0.0400

Gnomad4 AMR AF: 0.0472

Gnomad4 ASJ AF: 0.0628

Gnomad4 EAS AF: 0.0857

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.0612

Gnomad4 OTH AF: 0.0525

Alfa AF: 0.0515 Hom.: 93

Bravo AF: 0.0553

Asia WGS AF: 0.162 AC: 563 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 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.4
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17885803; hg19: chr17-7592482;