17-7688193-CG-CGG

Variant names:

• chr17-7688193-C-CG
• rs17551157
• ENST00000316024.9:c.-449dupG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000316024.9(WRAP53):​c.-449dupG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 182,602 control chromosomes in the GnomAD database, including 2,377 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (2222 hom., cov: 30)
  • Exomes 𝑓: 0.085 (155 hom.)
• Consequence: WRAP53 ENST00000316024.9 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.171
• Publications: 1 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• dyskeratosis congenita

  Inheritance: AR, AD Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 17-7688193-C-CG is Benign according to our data. Variant chr17-7688193-C-CG is described in ClinVar as Benign. ClinVar VariationId is 1182360.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000316024.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WRAP53	NM_001143990.2		c.-1-448dupG		intron	N/A	NP_001137462.1
	WRAP53	NM_001143991.2		c.-1-448dupG		intron	N/A	NP_001137463.1
	WRAP53	NM_018081.2		c.-456_-455insG		upstream_gene	N/A	NP_060551.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WRAP53	ENST00000316024.9	TSL:1	c.-449dupG		5_prime_UTR	Exon 1 of 10	ENSP00000324203.5
	WRAP53	ENST00000431639.6	TSL:1	c.-1-448dupG		intron	N/A	ENSP00000397219.2
	WRAP53	ENST00000457584.6	TSL:1	c.-1-448dupG		intron	N/A	ENSP00000411061.2

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21753 AN: 151834 Hom.: 2218 Cov.: 30

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.0454

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0714

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.0850 AC: 2606 AN: 30650 Hom.: 155 Cov.: 0 AF XY: 0.0929 AC XY: 1495 AN XY: 16088

African (AFR) AF: 0.152 AC: 66 AN: 434

American (AMR) AF: 0.137 AC: 435 AN: 3184

Ashkenazi Jewish (ASJ) AF: 0.0496 AC: 26 AN: 524

East Asian (EAS) AF: 0.193 AC: 194 AN: 1006

South Asian (SAS) AF: 0.155 AC: 733 AN: 4742

European-Finnish (FIN) AF: 0.0347 AC: 40 AN: 1154

Middle Eastern (MID) AF: 0.0441 AC: 3 AN: 68

European-Non Finnish (NFE) AF: 0.0553 AC: 992 AN: 17926

Other (OTH) AF: 0.0726 AC: 117 AN: 1612

GnomAD4 genome AF: 0.143 AC: 21788 AN: 151952 Hom.: 2222 Cov.: 30 AF XY: 0.143 AC XY: 10657 AN XY: 74272

African (AFR) AF: 0.270 AC: 11209 AN: 41450

American (AMR) AF: 0.137 AC: 2084 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3468

East Asian (EAS) AF: 0.304 AC: 1564 AN: 5144

South Asian (SAS) AF: 0.205 AC: 980 AN: 4786

European-Finnish (FIN) AF: 0.0454 AC: 481 AN: 10598

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0714 AC: 4853 AN: 67944

Other (OTH) AF: 0.126 AC: 266 AN: 2112

Alfa AF: 0.0367 Hom.: 23

Bravo AF: 0.153

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.17
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17551157; hg19: chr17-7591511;