rs587778642
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000321.3(RB1):c.2260G>A(p.Val754Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000074 in 1,350,728 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. V754L) 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.2260G>A | p.Val754Ile | missense_variant | 22/27 | ENST00000267163.6 | |
RB1 | NM_001407165.1 | c.2260G>A | p.Val754Ile | missense_variant | 22/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.2260G>A | p.Val754Ile | missense_variant | 22/27 | 1 | NM_000321.3 | P1 | |
RB1 | ENST00000650461.1 | c.2260G>A | p.Val754Ile | missense_variant | 22/27 | ||||
RB1 | ENST00000643064.1 | c.194+83603G>A | intron_variant |
Frequencies
GnomAD3 genomes ? Cov.: 28
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251318Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135868
GnomAD4 exome AF: 7.40e-7 AC: 1AN: 1350728Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 670438
GnomAD4 genome ? Cov.: 28
ClinVar
Submissions by phenotype
Retinoblastoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Diagnostic Laboratory, University of Pennsylvania School of Medicine | May 20, 2024 | Case and Pedigree Information: BILATERAL CASES:0, UNILATERAL CASES:1, TOTAL CASES:1, PEDIGREES:1. ACMG Codes Applied:PM1, PM2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at