13-48303964-G-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000321.3(RB1):c.52G>T(p.Ala18Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,509,556 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A18T) has been classified as Uncertain significance.
Frequency
Consequence
NM_000321.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.52G>T | p.Ala18Ser | missense_variant | 1/27 | ENST00000267163.6 | |
RB1 | NM_001407165.1 | c.52G>T | p.Ala18Ser | missense_variant | 1/27 | ||
RB1 | NM_001407166.1 | c.52G>T | p.Ala18Ser | missense_variant | 1/17 | ||
RB1 | NM_001407167.1 | c.52G>T | p.Ala18Ser | missense_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.52G>T | p.Ala18Ser | missense_variant | 1/27 | 1 | NM_000321.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000711 AC: 108AN: 151826Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000663 AC: 7AN: 105654Hom.: 0 AF XY: 0.0000679 AC XY: 4AN XY: 58918
GnomAD4 exome AF: 0.0000759 AC: 103AN: 1357622Hom.: 1 Cov.: 31 AF XY: 0.0000687 AC XY: 46AN XY: 669730
GnomAD4 genome AF: 0.000711 AC: 108AN: 151934Hom.: 0 Cov.: 32 AF XY: 0.000511 AC XY: 38AN XY: 74292
ClinVar
Submissions by phenotype
Retinoblastoma Benign:2
Benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jan 04, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 07, 2018 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at