13-48303757-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000321.3(RB1):​c.-156C>G variant causes a 5 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

RB1
NM_000321.3 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.419
Variant links:
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-DT (HGNC:42778): (RB1 divergent transcript)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.26).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RB1NM_000321.3 linkc.-156C>G 5_prime_UTR_variant Exon 1 of 27 ENST00000267163.6 NP_000312.2 P06400A0A024RDV3
RB1NM_001407165.1 linkc.-156C>G 5_prime_UTR_variant Exon 1 of 27 NP_001394094.1
RB1NM_001407166.1 linkc.-156C>G 5_prime_UTR_variant Exon 1 of 17 NP_001394095.1
RB1NM_001407167.1 linkc.-156C>G 5_prime_UTR_variant Exon 1 of 3 NP_001394096.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RB1ENST00000267163 linkc.-156C>G 5_prime_UTR_variant Exon 1 of 27 1 NM_000321.3 ENSP00000267163.4 P06400

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
14
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.26
CADD
Benign
18
DANN
Benign
0.96

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-48877893; API