rs766529534
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2
The NM_000321.3(RB1):c.113G>A(p.Gly38Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000182 in 1,464,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G38S) 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 -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.113G>A | p.Gly38Asp | missense_variant | 1/27 | ENST00000267163.6 | |
RB1 | NM_001407165.1 | c.113G>A | p.Gly38Asp | missense_variant | 1/27 | ||
RB1 | NM_001407166.1 | c.113G>A | p.Gly38Asp | missense_variant | 1/17 | ||
RB1 | NM_001407167.1 | c.113G>A | p.Gly38Asp | missense_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.113G>A | p.Gly38Asp | missense_variant | 1/27 | 1 | NM_000321.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152118Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000159 AC: 11AN: 69018Hom.: 0 AF XY: 0.000198 AC XY: 8AN XY: 40396
GnomAD4 exome AF: 0.000187 AC: 245AN: 1312602Hom.: 0 Cov.: 31 AF XY: 0.000193 AC XY: 125AN XY: 646844
GnomAD4 genome ? AF: 0.000145 AC: 22AN: 152118Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74318
ClinVar
Submissions by phenotype
Retinoblastoma Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Nov 03, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 10, 2018 | This alteration is classified as likely 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. - |
RB1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 02, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at