Variant rs4987239 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000553.6(WRN):c.355+20A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 1,612,694 control chromosomes in the GnomAD database, including 2,926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 184 hom., cov: 33)

Exomes 𝑓: 0.058 ( 2742 hom. )

Consequence

WRN
NM_000553.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.140

Variant links:

Genes affected

WRN (HGNC:12791): (WRN RecQ like helicase) This gene encodes a member of the RecQ subfamily of DNA helicase proteins. The encoded nuclear protein is important in the maintenance of genome stability and plays a role in DNA repair, replication, transcription and telomere maintenance. This protein contains a N-terminal 3' to 5' exonuclease domain, an ATP-dependent helicase domain and RQC (RecQ helicase conserved region) domain in its central region, and a C-terminal HRDC (helicase RNase D C-terminal) domain and nuclear localization signal. Defects in this gene are the cause of Werner syndrome, an autosomal recessive disorder characterized by accelerated aging and an elevated risk for certain cancers. [provided by RefSeq, Aug 2017]

WRN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 8-31064454-A-T is Benign according to our data. Variant chr8-31064454-A-T is described in ClinVar as [Benign]. Clinvar id is 256709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-31064454-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WRN	NM_000553.6 linkuse as main transcript	c.355+20A>T		intron_variant		ENST00000298139.7	NP_000544.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WRN	ENST00000298139.7 linkuse as main transcript	c.355+20A>T		intron_variant		1	NM_000553.6	ENSP00000298139	P1
WRN	ENST00000650667.1 linkuse as main transcript	c.210-461A>T		intron_variant, NMD_transcript_variant				ENSP00000498593

Frequencies

GnomAD3 genomes

AF:

0.0447

AC:

6804

AN:

152122

Hom.:

183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0166

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.0305

Gnomad ASJ

AF:

0.0452

Gnomad EAS

AF:

0.0237

Gnomad SAS

AF:

0.0793

Gnomad FIN

AF:

0.0695

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0596

Gnomad OTH

AF:

0.0431

GnomAD3 exomes

AF:

0.0496

AC:

12456

AN:

251284

Hom.:

404

AF XY:

0.0519

AC XY:

7047

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.0149

Gnomad AMR exome

AF:

0.0202

Gnomad ASJ exome

AF:

0.0441

Gnomad EAS exome

AF:

0.0213

Gnomad SAS exome

AF:

0.0779

Gnomad FIN exome

AF:

0.0682

Gnomad NFE exome

AF:

0.0576

Gnomad OTH exome

AF:

0.0452

GnomAD4 exome

AF:

0.0583

AC:

85146

AN:

1460454

Hom.:

2742

Cov.:

AF XY:

0.0592

AC XY:

42992

AN XY:

726572

show subpopulations

Gnomad4 AFR exome

AF:

0.0141

Gnomad4 AMR exome

AF:

0.0213

Gnomad4 ASJ exome

AF:

0.0444

Gnomad4 EAS exome

AF:

0.0231

Gnomad4 SAS exome

AF:

0.0752

Gnomad4 FIN exome

AF:

0.0664

Gnomad4 NFE exome

AF:

0.0613

Gnomad4 OTH exome

AF:

0.0534

GnomAD4 genome

AF:

0.0447

AC:

6806

AN:

152240

Hom.:

184

Cov.:

AF XY:

0.0451

AC XY:

3358

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0166

Gnomad4 AMR

AF:

0.0305

Gnomad4 ASJ

AF:

0.0452

Gnomad4 EAS

AF:

0.0235

Gnomad4 SAS

AF:

0.0798

Gnomad4 FIN

AF:

0.0695

Gnomad4 NFE

AF:

0.0596

Gnomad4 OTH

AF:

0.0432

Alfa

AF:

0.0508

Hom.:

Bravo

AF:

0.0394

Asia WGS

AF:

0.0550

AC:

191

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Werner syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 03, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Wiskott-Aldrich syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.4

DANN

Benign

0.54

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