chr13-48303700-C-T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000433480.4(RB1-DT):n.24G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 717,346 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000053 ( 0 hom. )
Consequence
RB1-DT
ENST00000433480.4 non_coding_transcript_exon
ENST00000433480.4 non_coding_transcript_exon
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 3.01
Publications
0 publications found
Genes affected
RB1-DT (HGNC:42778): (RB1 divergent transcript)
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), G2P, Ambry Genetics
- 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: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.23).
Variant Effect in Transcripts
ACMG analysis was done for transcript: ENST00000433480.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RB1-DT | NR_046414.2 | n.3G>A | non_coding_transcript_exon | Exon 1 of 3 | |||||
| RB1 | NM_000321.3 | MANE Select | c.-213C>T | upstream_gene | N/A | NP_000312.2 | P06400 | ||
| RB1 | NM_001407165.1 | c.-213C>T | upstream_gene | N/A | NP_001394094.1 | A0A3B3IS71 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RB1-DT | ENST00000433480.4 | TSL:1 | n.24G>A | non_coding_transcript_exon | Exon 1 of 3 | ||||
| RB1-DT | ENST00000436963.3 | TSL:3 | n.21G>A | non_coding_transcript_exon | Exon 1 of 3 | ||||
| RB1-DT | ENST00000700890.2 | n.24G>A | non_coding_transcript_exon | Exon 1 of 3 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152162Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152162
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000531 AC: 3AN: 565184Hom.: 0 Cov.: 8 AF XY: 0.00000345 AC XY: 1AN XY: 289448 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
3
AN:
565184
Hom.:
Cov.:
8
AF XY:
AC XY:
1
AN XY:
289448
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
10976
American (AMR)
AF:
AC:
0
AN:
10404
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
13084
East Asian (EAS)
AF:
AC:
0
AN:
24284
South Asian (SAS)
AF:
AC:
0
AN:
43434
European-Finnish (FIN)
AF:
AC:
0
AN:
28110
Middle Eastern (MID)
AF:
AC:
0
AN:
2102
European-Non Finnish (NFE)
AF:
AC:
3
AN:
404112
Other (OTH)
AF:
AC:
0
AN:
28678
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000000000965894), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.292
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.00000657 AC: 1AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74336 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152162
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74336
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41456
American (AMR)
AF:
AC:
0
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5198
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67980
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.675
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Retinoblastoma (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Uncertain
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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