13-48452997-C-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000321.3(RB1):c.1700C>G(p.Ser567Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. S567S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000321.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.1700C>G | p.Ser567Ter | stop_gained | 18/27 | ENST00000267163.6 | |
RB1 | NM_001407165.1 | c.1700C>G | p.Ser567Ter | stop_gained | 18/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.1700C>G | p.Ser567Ter | stop_gained | 18/27 | 1 | NM_000321.3 | P1 | |
RB1 | ENST00000650461.1 | c.1700C>G | p.Ser567Ter | stop_gained | 18/27 | ||||
RB1 | ENST00000643064.1 | c.194+71554C>G | intron_variant | ||||||
RB1 | ENST00000480491.1 | n.399C>G | non_coding_transcript_exon_variant | 2/3 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Retinoblastoma Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2023 | This sequence change creates a premature translational stop signal (p.Ser567*) in the RB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RB1 are known to be pathogenic (PMID: 17096365). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RB1-related conditions. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.