rs3213199

Positions:

• chr8-31108475-T-A
• chr8-31108475-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000553.6(WRN):​c.2089-3140T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 151,670 control chromosomes in the GnomAD database, including 1,507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1507 hom., cov: 32)
• Consequence: WRN NM_000553.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 8-31108475-T-A is Benign according to our data. Variant chr8-31108475-T-A is described in ClinVar as [Benign]. Clinvar id is 1289082.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WRN	NM_000553.6	c.2089-3140T>A		intron_variant		ENST00000298139.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WRN	ENST00000298139.7	c.2089-3140T>A		intron_variant		1	NM_000553.6	P1
WRN	ENST00000521620.5	n.722-3140T>A		intron_variant, non_coding_transcript_variant		1
WRN	ENST00000650667.1	c.*1703-3140T>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19201 AN: 151550 Hom.: 1506 Cov.: 32

Gnomad AFR AF: 0.0352

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0719

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.130

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.127 AC: 19214 AN: 151670 Hom.: 1507 Cov.: 32 AF XY: 0.127 AC XY: 9452 AN XY: 74170

Gnomad4 AFR AF: 0.0354

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.0717

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.129

Alfa AF: 0.0777 Hom.: 109

Bravo AF: 0.117

Asia WGS AF: 0.110 AC: 382 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.047
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs3213199; hg19: chr8-30965991;