8-31166927-C-T
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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
NM_000553.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.282
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]
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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 |
---|---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.3983-95C>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.3983-95C>T | intron_variant | 1 | NM_000553.6 | ENSP00000298139.5 | ||||
WRN | ENST00000521620.5 | n.2616-95C>T | intron_variant | 1 | ||||||
WRN | ENST00000650667.1 | n.*3597-95C>T | intron_variant | ENSP00000498593.1 | ||||||
WRN | ENST00000651946.1 | n.207-95C>T | intron_variant |
Frequencies
GnomAD3 genomes AF: 0.278 AC: 42152AN: 151842Hom.: 6062 Cov.: 32
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GnomAD4 exome AF: 0.289 AC: 318143AN: 1101948Hom.: 46859 AF XY: 0.291 AC XY: 160441AN XY: 552096
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GnomAD4 genome AF: 0.277 AC: 42160AN: 151960Hom.: 6065 Cov.: 32 AF XY: 0.281 AC XY: 20877AN XY: 74248
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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 submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 21, 2018 | - - |
Computational scores
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Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at