rs761609284

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000321.3(RB1):​c.850A>C​(p.Asn284His) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,258 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

RB1
NM_000321.3 missense

Scores

1
13
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.52
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RB1NM_000321.3 linkc.850A>C p.Asn284His missense_variant Exon 8 of 27 ENST00000267163.6 NP_000312.2 P06400A0A024RDV3
RB1NM_001407165.1 linkc.850A>C p.Asn284His missense_variant Exon 8 of 27 NP_001394094.1
RB1NM_001407166.1 linkc.850A>C p.Asn284His missense_variant Exon 8 of 17 NP_001394095.1
LOC112268118XR_002957522.2 linkn.*242T>G downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RB1ENST00000267163.6 linkc.850A>C p.Asn284His missense_variant Exon 8 of 27 1 NM_000321.3 ENSP00000267163.4 P06400
RB1ENST00000650461.1 linkc.850A>C p.Asn284His missense_variant Exon 8 of 27 ENSP00000497193.1 A0A3B3IS71
RB1ENST00000467505.5 linkn.*218A>C downstream_gene_variant 1 ENSP00000434702.1 Q92728

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152258
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:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152258
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74386
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:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.54
D;.
Eigen
Uncertain
0.65
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.079
D
MetaRNN
Uncertain
0.47
T;T
MetaSVM
Uncertain
0.72
D
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-1.9
N;.
REVEL
Uncertain
0.48
Sift
Benign
0.14
T;.
Sift4G
Uncertain
0.0060
D;.
Polyphen
1.0
D;.
Vest4
0.66
MutPred
0.35
Gain of catalytic residue at E280 (P = 0);Gain of catalytic residue at E280 (P = 0);
MVP
0.88
MPC
0.90
ClinPred
0.91
D
GERP RS
6.2
Varity_R
0.28
gMVP
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs761609284; hg19: chr13-48937082; API