rs2725361

chr8-31139810-A-Gchr8-31139810-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000553.6(WRN):c.2968-1620A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,928 control chromosomes in the GnomAD database, including 9,171 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 0.33 (9171 hom., cov: 30)
• Consequence: WRN NM_000553.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WRN	NM_000553.6	c.2968-1620A>G		intron_variant		ENST00000298139.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WRN	ENST00000298139.7	c.2968-1620A>G		intron_variant		1	NM_000553.6	P1
WRN	ENST00000521620.5	n.1601-1620A>G		intron_variant, non_coding_transcript_variant		1
WRN	ENST00000650667.1	c.*2582-1620A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50040 AN: 151810 Hom.: 9166 Cov.: 30

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.330 AC: 50062 AN: 151928 Hom.: 9171 Cov.: 30 AF XY: 0.328 AC XY: 24375 AN XY: 74226

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.356

Alfa AF: 0.356 Hom.: 5559

Bravo AF: 0.343

Asia WGS AF: 0.441 AC: 1530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.1
Dann	Benign	0.61

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: rs2725361; hg19: chr8-30997326;