rs1060503067
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000321.3(RB1):c.2029G>A(p.Glu677Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,010 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E677G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000321.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.2029G>A | p.Glu677Lys | missense_variant | 20/27 | ENST00000267163.6 | |
RB1 | NM_001407165.1 | c.2029G>A | p.Glu677Lys | missense_variant | 20/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.2029G>A | p.Glu677Lys | missense_variant | 20/27 | 1 | NM_000321.3 | P1 | |
RB1 | ENST00000650461.1 | c.2029G>A | p.Glu677Lys | missense_variant | 20/27 | ||||
RB1 | ENST00000643064.1 | c.194+78313G>A | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152010Hom.: 0 Cov.: 30
GnomAD4 exome Cov.: 34
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152010Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74246
ClinVar
Submissions by phenotype
Retinoblastoma Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 03, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 677 of the RB1 protein (p.Glu677Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 883471). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at