chr8-31125006-G-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_000553.6(WRN):c.2825+6G>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,610,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
WRN
NM_000553.6 splice_donor_region, intron
NM_000553.6 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00006024
2
Clinical Significance
Conservation
PhyloP100: 0.0230
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 8-31125006-G-T is Benign according to our data. Variant chr8-31125006-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 238141.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WRN | NM_000553.6 | c.2825+6G>T | splice_donor_region_variant, intron_variant | ENST00000298139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WRN | ENST00000298139.7 | c.2825+6G>T | splice_donor_region_variant, intron_variant | 1 | NM_000553.6 | P1 | |||
WRN | ENST00000521620.5 | n.1458+6G>T | splice_donor_region_variant, intron_variant, non_coding_transcript_variant | 1 | |||||
WRN | ENST00000650667.1 | c.*2439+6G>T | splice_donor_region_variant, intron_variant, NMD_transcript_variant | ||||||
WRN | ENST00000520169.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000237 AC: 36AN: 152012Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000798 AC: 20AN: 250652Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135506
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GnomAD4 exome AF: 0.0000254 AC: 37AN: 1458442Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 18AN XY: 725674
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GnomAD4 genome AF: 0.000237 AC: 36AN: 152128Hom.: 0 Cov.: 31 AF XY: 0.000215 AC XY: 16AN XY: 74402
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Werner syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 12, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at