rs9535023
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PM2PP3_ModeratePP5_Very_Strong
The NM_000321.3(RB1):c.1390-14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Genomes: not found (cov: 29)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RB1
NM_000321.3 intron
NM_000321.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.649
Publications
10 publications found
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]
RB1 Gene-Disease associations (from GenCC):
- hereditary retinoblastomaInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
- retinoblastomaInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- melanomaInheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
Variant 13-48380039-A-G is Pathogenic according to our data. Variant chr13-48380039-A-G is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 410932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000321.3. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
29
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1097042Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0AN XY: 549002
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1097042
Hom.:
Cov.:
19
AF XY:
AC XY:
0
AN XY:
549002
African (AFR)
AF:
AC:
0
AN:
23056
American (AMR)
AF:
AC:
0
AN:
20820
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19614
East Asian (EAS)
AF:
AC:
0
AN:
29274
South Asian (SAS)
AF:
AC:
0
AN:
62068
European-Finnish (FIN)
AF:
AC:
0
AN:
40524
Middle Eastern (MID)
AF:
AC:
0
AN:
3130
European-Non Finnish (NFE)
AF:
AC:
0
AN:
853402
Other (OTH)
AF:
AC:
0
AN:
45154
GnomAD4 genome
GnomAD4 genome
Cov.:
29
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic/Likely pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
2
-
-
Retinoblastoma (2)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 1
DS_AL_spliceai
Position offset: 14
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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