13-48303757-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting

The NM_000321.3(RB1):​c.-156C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000582 in 1,202,008 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: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

RB1
NM_000321.3 5_prime_UTR_premature_start_codon_gain

Scores

1
1

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 Likely_benign. Variant got -3 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.24).
BS2
High AC in GnomAdExome4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RB1NM_000321.3 linkc.-156C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 27 ENST00000267163.6 NP_000312.2 P06400A0A024RDV3
RB1NM_000321.3 linkc.-156C>T 5_prime_UTR_variant Exon 1 of 27 ENST00000267163.6 NP_000312.2 P06400A0A024RDV3

Ensembl

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

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152112
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000571
AC:
6
AN:
1049896
Hom.:
0
Cov.:
14
AF XY:
0.00000193
AC XY:
1
AN XY:
517348
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000377
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000601
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152112
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000132
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.24
CADD
Benign
19
DANN
Uncertain
0.98

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs886050265; hg19: chr13-48877893; API