rs520342
Positions:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000321.3(RB1):c.380+45C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000169 in 1,181,046 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 0.0000017 ( 0 hom. )
Consequence
RB1
NM_000321.3 intron
NM_000321.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.96
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_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.380+45C>G | intron_variant | ENST00000267163.6 | |||
RB1 | NM_001407165.1 | c.380+45C>G | intron_variant | ||||
RB1 | NM_001407166.1 | c.380+45C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.380+45C>G | intron_variant | 1 | NM_000321.3 | P1 | |||
RB1 | ENST00000467505.5 | c.138-17258C>G | intron_variant, NMD_transcript_variant | 1 | |||||
RB1 | ENST00000650461.1 | c.380+45C>G | intron_variant | ||||||
RB1 | ENST00000525036.1 | n.542+45C>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000419 AC: 1AN: 238912Hom.: 0 AF XY: 0.00000770 AC XY: 1AN XY: 129830
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GnomAD4 exome AF: 0.00000169 AC: 2AN: 1181046Hom.: 0 Cov.: 16 AF XY: 0.00000333 AC XY: 2AN XY: 600118
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GnomAD4 genome ? Cov.: 32
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?
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32
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at