chr13-48453505-G-A
Variant names:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_000321.3(RB1):c.1814+394G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 152,310 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.017 ( 48 hom., cov: 32)
Consequence
RB1
NM_000321.3 intron
NM_000321.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.76
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 was made for transcript
Our verdict: Benign. The variant received -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BS1
Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0168 (2560/152310) while in subpopulation AMR AF = 0.0436 (666/15292). AF 95% confidence interval is 0.0408. There are 48 homozygotes in GnomAd4. There are 1245 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
BS2
High AC in GnomAd4 at 2560 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.1814+394G>A | intron_variant | Intron 18 of 26 | ENST00000267163.6 | NP_000312.2 | ||
RB1 | NM_001407165.1 | c.1814+394G>A | intron_variant | Intron 18 of 26 | NP_001394094.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.1814+394G>A | intron_variant | Intron 18 of 26 | 1 | NM_000321.3 | ENSP00000267163.4 | |||
RB1 | ENST00000650461.1 | c.1814+394G>A | intron_variant | Intron 18 of 26 | ENSP00000497193.1 | |||||
RB1 | ENST00000643064.1 | c.192+72062G>A | intron_variant | Intron 1 of 1 | ENSP00000496005.1 | |||||
RB1 | ENST00000480491.1 | n.513+394G>A | intron_variant | Intron 2 of 2 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0168 AC: 2559AN: 152192Hom.: 48 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
2559
AN:
152192
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
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Gnomad NFE
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Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.0168 AC: 2560AN: 152310Hom.: 48 Cov.: 32 AF XY: 0.0167 AC XY: 1245AN XY: 74474 show subpopulations
GnomAD4 genome
AF:
AC:
2560
AN:
152310
Hom.:
Cov.:
32
AF XY:
AC XY:
1245
AN XY:
74474
Gnomad4 AFR
AF:
AC:
0.00471449
AN:
0.00471449
Gnomad4 AMR
AF:
AC:
0.0435522
AN:
0.0435522
Gnomad4 ASJ
AF:
AC:
0.0100865
AN:
0.0100865
Gnomad4 EAS
AF:
AC:
0.000385505
AN:
0.000385505
Gnomad4 SAS
AF:
AC:
0.008285
AN:
0.008285
Gnomad4 FIN
AF:
AC:
0.0147834
AN:
0.0147834
Gnomad4 NFE
AF:
AC:
0.0211562
AN:
0.0211562
Gnomad4 OTH
AF:
AC:
0.0108798
AN:
0.0108798
Heterozygous variant carriers
0
133
266
399
532
665
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
28
56
84
112
140
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
20
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
Mutation Taster
=100/0
polymorphism
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at