17-7689164-C-T

Variant names:

• chr17-7689164-C-T
• rs17885803
• NM_001143992.2:c.432-60C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• dyskeratosis congenita, autosomal recessive 3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• dyskeratosis congenita

  Inheritance: AD, Unknown Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• telomere syndrome

  Inheritance: SD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143992.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WRAP53	NM_001143992.2	MANE Select	c.432-60C>T		intron	N/A	NP_001137464.1	Q9BUR4
	WRAP53	NM_001143990.2		c.432-60C>T		intron	N/A	NP_001137462.1	Q9BUR4
	WRAP53	NM_001143991.2		c.432-60C>T		intron	N/A	NP_001137463.1	Q9BUR4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WRAP53	ENST00000396463.7	TSL:1 MANE Select	c.432-60C>T		intron	N/A	ENSP00000379727.3	Q9BUR4
	WRAP53	ENST00000316024.9	TSL:1	c.432-60C>T		intron	N/A	ENSP00000324203.5	Q9BUR4
	WRAP53	ENST00000431639.6	TSL:1	c.432-60C>T		intron	N/A	ENSP00000397219.2	Q9BUR4

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

African (AFR) AF: 0.0390 AC: 1306 AN: 33466

American (AMR) AF: 0.0559 AC: 2497 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.0575 AC: 1502 AN: 26132

East Asian (EAS) AF: 0.0749 AC: 2974 AN: 39692

South Asian (SAS) AF: 0.163 AC: 14079 AN: 86242

European-Finnish (FIN) AF: 0.116 AC: 6206 AN: 53402

Middle Eastern (MID) AF: 0.0421 AC: 243 AN: 5768

European-Non Finnish (NFE) AF: 0.0637 AC: 70813 AN: 1111520

Other (OTH) AF: 0.0686 AC: 4141 AN: 60384

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

African (AFR) AF: 0.0400 AC: 1658 AN: 41432

American (AMR) AF: 0.0472 AC: 721 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0628 AC: 218 AN: 3470

East Asian (EAS) AF: 0.0857 AC: 442 AN: 5158

South Asian (SAS) AF: 0.162 AC: 779 AN: 4796

European-Finnish (FIN) AF: 0.118 AC: 1247 AN: 10538

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0612 AC: 4161 AN: 67970

Other (OTH) AF: 0.0525 AC: 111 AN: 2116

Alfa AF: 0.0559 Hom.: 161

Bravo AF: 0.0553

Asia WGS AF: 0.162 AC: 563 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.4
DANN	Benign	0.71
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17885803; hg19: chr17-7592482; COSMIC: COSV107296020; COSMIC: COSV107296020;