rs748093967
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_000321.3(RB1):c.342G>A(p.Ser114Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,611,650 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
RB1
NM_000321.3 synonymous
NM_000321.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0450
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 -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 13-48342676-G-A is Benign according to our data. Variant chr13-48342676-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 237672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.045 with no splicing effect.
BS2
High AC in GnomAdExome4 at 19 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.342G>A | p.Ser114Ser | synonymous_variant | 3/27 | ENST00000267163.6 | NP_000312.2 | |
RB1 | NM_001407165.1 | c.342G>A | p.Ser114Ser | synonymous_variant | 3/27 | NP_001394094.1 | ||
RB1 | NM_001407166.1 | c.342G>A | p.Ser114Ser | synonymous_variant | 3/17 | NP_001394095.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.342G>A | p.Ser114Ser | synonymous_variant | 3/27 | 1 | NM_000321.3 | ENSP00000267163.4 | ||
RB1 | ENST00000467505.5 | n.138-17341G>A | intron_variant | 1 | ENSP00000434702.1 | |||||
RB1 | ENST00000650461.1 | c.342G>A | p.Ser114Ser | synonymous_variant | 3/27 | ENSP00000497193.1 | ||||
RB1 | ENST00000525036.1 | n.504G>A | non_coding_transcript_exon_variant | 3/7 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151998Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251172Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135782
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1459652Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 726254
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 151998Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74252
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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
Retinoblastoma Benign:2
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Sep 04, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 21, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 07, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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