rs587776785
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1PP5
The NM_000321.3(RB1):c.1949_1957del(p.Phe650_Lys653delinsTer) variant causes a stop gained, inframe deletion change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
RB1
NM_000321.3 stop_gained, inframe_deletion
NM_000321.3 stop_gained, inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.43
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 Likely_pathogenic. Variant got 9 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 13-48456337-TTTTATAAAA-T is Pathogenic according to our data. Variant chr13-48456337-TTTTATAAAA-T is described in ClinVar as [Pathogenic]. Clinvar id is 13083.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr13-48456337-TTTTATAAAA-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.1949_1957del | p.Phe650_Lys653delinsTer | stop_gained, inframe_deletion | 19/27 | ENST00000267163.6 | |
RB1 | NM_001407165.1 | c.1949_1957del | p.Phe650_Lys653delinsTer | stop_gained, inframe_deletion | 19/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.1949_1957del | p.Phe650_Lys653delinsTer | stop_gained, inframe_deletion | 19/27 | 1 | NM_000321.3 | P1 | |
RB1 | ENST00000650461.1 | c.1949_1957del | p.Phe650_Lys653delinsTer | stop_gained, inframe_deletion | 19/27 | ||||
RB1 | ENST00000643064.1 | c.194+74895_194+74903del | intron_variant | ||||||
RB1 | ENST00000480491.1 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Retinoblastoma Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 1989 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at