rs145080962
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_000553.6(WRN):c.1577-17T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000658 in 1,601,474 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0034 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00037 ( 3 hom. )
Consequence
WRN
NM_000553.6 intron
NM_000553.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.75
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 -16 ACMG points.
BP6
Variant 8-31088873-T-G is Benign according to our data. Variant chr8-31088873-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 256706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00337 (513/152204) while in subpopulation AFR AF= 0.0117 (488/41562). AF 95% confidence interval is 0.0109. There are 2 homozygotes in gnomad4. There are 249 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.1577-17T>G | intron_variant | ENST00000298139.7 | NP_000544.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.1577-17T>G | intron_variant | 1 | NM_000553.6 | ENSP00000298139.5 | ||||
WRN | ENST00000521620.5 | n.278-17T>G | intron_variant | 1 | ||||||
WRN | ENST00000650667.1 | n.*1191-17T>G | intron_variant | ENSP00000498593.1 |
Frequencies
GnomAD3 genomes AF: 0.00336 AC: 511AN: 152086Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000988 AC: 235AN: 237868Hom.: 1 AF XY: 0.000679 AC XY: 87AN XY: 128090
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GnomAD4 exome AF: 0.000373 AC: 540AN: 1449270Hom.: 3 Cov.: 30 AF XY: 0.000314 AC XY: 226AN XY: 720056
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GnomAD4 genome AF: 0.00337 AC: 513AN: 152204Hom.: 2 Cov.: 32 AF XY: 0.00335 AC XY: 249AN XY: 74412
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Werner syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 29, 2019 | - - |
Wiskott-Aldrich syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at