Variant 17-7689462-G-A 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.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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.439

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
WRAP53	NM_001143992.2 linkuse as main transcript	c.531-128G>A	intron_variant	ENST00000396463.7
WRAP53	NM_001143990.2 linkuse as main transcript	c.531-128G>A	intron_variant
WRAP53	NM_001143991.2 linkuse as main transcript	c.531-128G>A	intron_variant
WRAP53	NM_018081.2 linkuse as main transcript	c.531-128G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WRAP53	ENST00000396463.7 linkuse as main transcript	c.531-128G>A		intron_variant		1	NM_001143992.2	P1

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37400

AN:

151778

Hom.:

7714

Cov.:

show subpopulations

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.:

AF XY:

0.128

AC XY:

71484

AN XY:

556792

show subpopulations

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.:

AF XY:

0.242

AC XY:

17960

AN XY:

74268

show subpopulations

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:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

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