8-31166927-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000553.6(WRN):​c.3983-95C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,253,908 control chromosomes in the GnomAD database, including 52,924 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6065 hom., cov: 32)
Exomes 𝑓: 0.29 ( 46859 hom. )

Consequence

WRN
NM_000553.6 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.282
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 8-31166927-C-T is Benign according to our data. Variant chr8-31166927-C-T is described in ClinVar as [Benign]. Clinvar id is 1293737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WRNNM_000553.6 linkuse as main transcriptc.3983-95C>T intron_variant ENST00000298139.7 NP_000544.2 Q14191

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WRNENST00000298139.7 linkuse as main transcriptc.3983-95C>T intron_variant 1 NM_000553.6 ENSP00000298139.5 Q14191
WRNENST00000521620.5 linkuse as main transcriptn.2616-95C>T intron_variant 1
WRNENST00000650667.1 linkuse as main transcriptn.*3597-95C>T intron_variant ENSP00000498593.1 A0A494C0M3
WRNENST00000651946.1 linkuse as main transcriptn.207-95C>T intron_variant

Frequencies

GnomAD3 genomes
AF:
0.278
AC:
42152
AN:
151842
Hom.:
6062
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.228
Gnomad AMI
AF:
0.447
Gnomad AMR
AF:
0.264
Gnomad ASJ
AF:
0.309
Gnomad EAS
AF:
0.244
Gnomad SAS
AF:
0.338
Gnomad FIN
AF:
0.349
Gnomad MID
AF:
0.313
Gnomad NFE
AF:
0.294
Gnomad OTH
AF:
0.285
GnomAD4 exome
AF:
0.289
AC:
318143
AN:
1101948
Hom.:
46859
AF XY:
0.291
AC XY:
160441
AN XY:
552096
show subpopulations
Gnomad4 AFR exome
AF:
0.213
Gnomad4 AMR exome
AF:
0.250
Gnomad4 ASJ exome
AF:
0.308
Gnomad4 EAS exome
AF:
0.286
Gnomad4 SAS exome
AF:
0.332
Gnomad4 FIN exome
AF:
0.347
Gnomad4 NFE exome
AF:
0.285
Gnomad4 OTH exome
AF:
0.289
GnomAD4 genome
AF:
0.277
AC:
42160
AN:
151960
Hom.:
6065
Cov.:
32
AF XY:
0.281
AC XY:
20877
AN XY:
74248
show subpopulations
Gnomad4 AFR
AF:
0.228
Gnomad4 AMR
AF:
0.263
Gnomad4 ASJ
AF:
0.309
Gnomad4 EAS
AF:
0.244
Gnomad4 SAS
AF:
0.338
Gnomad4 FIN
AF:
0.349
Gnomad4 NFE
AF:
0.294
Gnomad4 OTH
AF:
0.285
Alfa
AF:
0.287
Hom.:
1031
Bravo
AF:
0.267
Asia WGS
AF:
0.290
AC:
1010
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJul 21, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
6.7
DANN
Benign
0.63

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4987036; hg19: chr8-31024443; API