chr13-48476750-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_000321.3(RB1):c.2570G>A(p.Arg857His) variant causes a missense change. The variant allele was found at a frequency of 0.0000583 in 1,613,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R857C) has been classified as Likely benign.
Frequency
Consequence
NM_000321.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.2570G>A | p.Arg857His | missense_variant | 25/27 | ENST00000267163.6 | |
RB1 | NM_001407165.1 | c.2570G>A | p.Arg857His | missense_variant | 25/27 | ||
RB1 | NM_001407168.1 | c.20G>A | p.Arg7His | missense_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.2570G>A | p.Arg857His | missense_variant | 25/27 | 1 | NM_000321.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000915 AC: 23AN: 251284Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135798
GnomAD4 exome AF: 0.0000520 AC: 76AN: 1461114Hom.: 0 Cov.: 30 AF XY: 0.0000550 AC XY: 40AN XY: 726884
GnomAD4 genome AF: 0.000118 AC: 18AN: 152270Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74462
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 01, 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. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Apr 29, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 14, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Retinoblastoma Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at