rs13251813

chr8-31106695-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000553.6(WRN):c.2089-4920C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0335 in 152,278 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.034 (175 hom., cov: 32)
• Consequence: WRN NM_000553.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0335 (5107/152278) while in subpopulation NFE AF= 0.0406 (2765/68024). AF 95% confidence interval is 0.0394. There are 175 homozygotes in gnomad4. There are 2727 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 175 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WRN	NM_000553.6	c.2089-4920C>T		intron_variant		ENST00000298139.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WRN	ENST00000298139.7	c.2089-4920C>T		intron_variant		1	NM_000553.6	P1
WRN	ENST00000521620.5	n.722-4920C>T		intron_variant, non_coding_transcript_variant		1
WRN	ENST00000650667.1	c.*1703-4920C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 5107 AN: 152160 Hom.: 175 Cov.: 32

Gnomad AFR AF: 0.00695

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.0216

Gnomad ASJ AF: 0.0521

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0406

Gnomad OTH AF: 0.0315

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

GnomAD4 genome AF: 0.0335 AC: 5107 AN: 152278 Hom.: 175 Cov.: 32 AF XY: 0.0366 AC XY: 2727 AN XY: 74454

Gnomad4 AFR AF: 0.00693

Gnomad4 AMR AF: 0.0216

Gnomad4 ASJ AF: 0.0521

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00414

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.0406

Gnomad4 OTH AF: 0.0312

Alfa AF: 0.0382 Hom.: 65

Bravo AF: 0.0255

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.3
Dann	Benign	0.45

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: rs13251813; hg19: chr8-30964211;