rs3092886
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000321.3(RB1):c.1216-29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00437 in 1,612,740 control chromosomes in the GnomAD database, including 265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.024 ( 155 hom., cov: 32)
Exomes 𝑓: 0.0024 ( 110 hom. )
Consequence
RB1
NM_000321.3 intron
NM_000321.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.555
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 13-48376889-A-G is Benign according to our data. Variant chr13-48376889-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 235730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0807 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.1216-29A>G | intron_variant | ENST00000267163.6 | |||
LOC112268118 | XR_002957522.2 | n.41-2649T>C | intron_variant, non_coding_transcript_variant | ||||
RB1 | NM_001407165.1 | c.1216-29A>G | intron_variant | ||||
RB1 | NM_001407166.1 | c.1216-29A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.1216-29A>G | intron_variant | 1 | NM_000321.3 | P1 | |||
RB1 | ENST00000650461.1 | c.1216-29A>G | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0237 AC: 3613AN: 152156Hom.: 156 Cov.: 32
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GnomAD3 exomes AF: 0.00626 AC: 1568AN: 250532Hom.: 55 AF XY: 0.00456 AC XY: 618AN XY: 135496
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GnomAD4 exome AF: 0.00235 AC: 3439AN: 1460466Hom.: 110 Cov.: 30 AF XY: 0.00206 AC XY: 1500AN XY: 726586
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GnomAD4 genome ? AF: 0.0237 AC: 3616AN: 152274Hom.: 155 Cov.: 32 AF XY: 0.0224 AC XY: 1665AN XY: 74454
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 19, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jun 15, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 23, 2018 | This variant is associated with the following publications: (PMID: 16343894, 27884173) - |
Retinoblastoma Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Feb 06, 2020 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at