dbSNP rs543830844: WRN:c.725-9delT (chr8-31076156-AT-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000553.6(WRN):c.725-9delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000689 in 1,586,546 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 1 hom. )

Consequence

WRN
NM_000553.6 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.540

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 -16 ACMG points.

BP6

Variant 8-31076156-AT-A is Benign according to our data. Variant chr8-31076156-AT-A is described in ClinVar as [Benign]. Clinvar id is 256711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00293 (446/152032) while in subpopulation AFR AF= 0.00981 (407/41470). AF 95% confidence interval is 0.00903. There are 2 homozygotes in gnomad4. There are 217 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WRN	NM_000553.6 link	c.725-9delT		intron_variant	Intron 7 of 34	ENST00000298139.7	NP_000544.2	Q14191

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
WRN	ENST00000298139.7 link	c.725-16delT	intron_variant	Intron 7 of 34	1	NM_000553.6	ENSP00000298139.5	Q14191
WRN	ENST00000651642.1 link	c.20-16delT	intron_variant	Intron 1 of 3			ENSP00000498779.1	A0A494C0Y6
WRN	ENST00000650667.1 link	n.*339-16delT	intron_variant	Intron 6 of 33			ENSP00000498593.1	A0A494C0M3

Frequencies

GnomAD3 genomes

AF:

0.00293

AC:

445

AN:

151914

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00982

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000961

AC:

241

AN:

250686

Hom.:

AF XY:

0.000752

AC XY:

102

AN XY:

135614

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000451

AC:

647

AN:

1434514

Hom.:

Cov.:

AF XY:

0.000435

AC XY:

311

AN XY:

715484

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.000809

Gnomad4 EAS exome

AF:

0.000127

Gnomad4 SAS exome

AF:

0.0000933

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000142

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.00293

AC:

446

AN:

152032

Hom.:

Cov.:

AF XY:

0.00292

AC XY:

217

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00981

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000348

Hom.:

Bravo

AF:

0.00353

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Werner syndrome

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Sep 29, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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