rs765386327
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_000321.3(RB1):c.2212-9C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00046 ( 0 hom., cov: 0)
Exomes 𝑓: 0.018 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RB1
NM_000321.3 splice_polypyrimidine_tract, intron
NM_000321.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0003631
2
Clinical Significance
Conservation
PhyloP100: -0.0290
Genes affected
RB1 (HGNC:9884): (RB transcriptional corepressor 1) The protein encoded by this gene is a negative regulator of the cell cycle and was the first tumor suppressor gene found. The encoded protein also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. The active, hypophosphorylated form of the protein binds transcription factor E2F1. Defects in this gene are a cause of childhood cancer retinoblastoma (RB), bladder cancer, and osteogenic sarcoma. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant 13-48464989-C-A is Benign according to our data. Variant chr13-48464989-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 727657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.2212-9C>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000267163.6 | |||
RB1 | NM_001407165.1 | c.2212-9C>A | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.2212-9C>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000321.3 | P1 | |||
RB1 | ENST00000643064.1 | c.194+83546C>A | intron_variant | ||||||
RB1 | ENST00000650461.1 | c.2212-9C>A | splice_polypyrimidine_tract_variant, intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 25AN: 54864Hom.: 0 Cov.: 0 FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0176 AC: 9129AN: 520076Hom.: 0 Cov.: 16 AF XY: 0.0157 AC XY: 4335AN XY: 275530
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.000455 AC: 25AN: 54892Hom.: 0 Cov.: 0 AF XY: 0.000346 AC XY: 9AN XY: 26030
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Retinoblastoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | - - |
RB1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 21, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
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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