rs6994361

Positions:

• chr8-31161169-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.3982+3639C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 151,974 control chromosomes in the GnomAD database, including 28,795 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 0.61 (28795 hom., cov: 31)
• Consequence: WRN NM_000553.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WRN	NM_000553.6	c.3982+3639C>T		intron_variant		ENST00000298139.7	NP_000544.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WRN	ENST00000298139.7	c.3982+3639C>T		intron_variant		1	NM_000553.6	ENSP00000298139	P1
WRN	ENST00000521620.5	n.2615+3639C>T		intron_variant, non_coding_transcript_variant		1
WRN	ENST00000650667.1	c.*3596+3639C>T		intron_variant, NMD_transcript_variant				ENSP00000498593

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92968 AN: 151856 Hom.: 28771 Cov.: 31

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.612 AC: 93034 AN: 151974 Hom.: 28795 Cov.: 31 AF XY: 0.615 AC XY: 45658 AN XY: 74290

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.603

Alfa AF: 0.613 Hom.: 59031

Bravo AF: 0.592

Asia WGS AF: 0.543 AC: 1891 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.7
DANN	Benign	0.52

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: rs6994361; hg19: chr8-31018685;