chr8-31063269-C-T

Position:

• chr8-31063269-C-T

Variant summary

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

The NM_000553.6(WRN):​c.210-1020C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,104 control chromosomes in the GnomAD database, including 31,545 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 0.64 (31545 hom., cov: 34)
• Consequence: WRN NM_000553.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WRN	NM_000553.6	c.210-1020C>T		intron_variant		ENST00000298139.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WRN	ENST00000298139.7	c.210-1020C>T		intron_variant		1	NM_000553.6	P1
WRN	ENST00000650667.1	c.210-1646C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.638 AC: 97040 AN: 151986 Hom.: 31529 Cov.: 34

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.638 AC: 97098 AN: 152104 Hom.: 31545 Cov.: 34 AF XY: 0.642 AC XY: 47746 AN XY: 74328

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.818

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.661

Gnomad4 OTH AF: 0.630

Alfa AF: 0.639 Hom.: 19749

Bravo AF: 0.640

Asia WGS AF: 0.726 AC: 2521 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.32
DANN	Benign	0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2015230; hg19: chr8-30920785;