Variant 17-7689164-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.293

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
WRAP53	NM_001143992.2 linkuse as main transcript	c.432-60C>T	intron_variant	ENST00000396463.7
WRAP53	NM_001143990.2 linkuse as main transcript	c.432-60C>T	intron_variant
WRAP53	NM_001143991.2 linkuse as main transcript	c.432-60C>T	intron_variant
WRAP53	NM_018081.2 linkuse as main transcript	c.432-60C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WRAP53	ENST00000396463.7 linkuse as main transcript	c.432-60C>T		intron_variant		1	NM_001143992.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0623

AC:

9457

AN:

151830

Hom.:

396

Cov.:

show subpopulations

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.:

AF XY:

0.0738

AC XY:

53639

AN XY:

726946

show subpopulations

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.:

AF XY:

0.0668

AC XY:

4958

AN XY:

74228

show subpopulations

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.:

Bravo

AF:

0.0553

Asia WGS

AF:

0.162

AC:

563

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over