8-31058158-A-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.-76-214A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0597 in 152,254 control chromosomes in the GnomAD database, including 284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.060 (284 hom., cov: 33)
• Consequence: WRN NM_000553.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.324

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=-0.87).
• BP6: Variant 8-31058158-A-C is Benign according to our data. Variant chr8-31058158-A-C is described in ClinVar as [Benign]. Clinvar id is 1250354.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.076 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WRN	NM_000553.6	c.-76-214A>C		intron_variant		ENST00000298139.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WRN	ENST00000298139.7	c.-76-214A>C		intron_variant		1	NM_000553.6	P1
WRN	ENST00000650667.1	c.-76-214A>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0597 AC: 9083 AN: 152134 Hom.: 283 Cov.: 33

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0389

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.0741

Gnomad SAS AF: 0.0822

Gnomad FIN AF: 0.0696

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0598

Gnomad OTH AF: 0.0603

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

GnomAD4 genome AF: 0.0597 AC: 9089 AN: 152254 Hom.: 284 Cov.: 33 AF XY: 0.0602 AC XY: 4479 AN XY: 74448

Gnomad4 AFR AF: 0.0613

Gnomad4 AMR AF: 0.0388

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.0743

Gnomad4 SAS AF: 0.0827

Gnomad4 FIN AF: 0.0696

Gnomad4 NFE AF: 0.0598

Gnomad4 OTH AF: 0.0597

Alfa AF: 0.0610 Hom.: 32

Bravo AF: 0.0567

Asia WGS AF: 0.0800 AC: 278 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

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.7
Dann	Benign	0.72

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: rs11574175; hg19: chr8-30915674;