chr13-48380211-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM1BS2
The NM_000321.3(RB1):c.1468G>A(p.Ala490Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,605,006 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A490S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000321.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.1468G>A | p.Ala490Thr | missense_variant | 16/27 | ENST00000267163.6 | |
RB1 | NM_001407165.1 | c.1468G>A | p.Ala490Thr | missense_variant | 16/27 | ||
RB1 | NM_001407166.1 | c.1468G>A | p.Ala490Thr | missense_variant | 16/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.1468G>A | p.Ala490Thr | missense_variant | 16/27 | 1 | NM_000321.3 | P1 | |
RB1 | ENST00000650461.1 | c.1468G>A | p.Ala490Thr | missense_variant | 16/27 |
Frequencies
GnomAD3 genomes AF: 0.0000133 AC: 2AN: 150198Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000242 AC: 6AN: 247962Hom.: 0 AF XY: 0.0000298 AC XY: 4AN XY: 134216
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1454706Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 723682
GnomAD4 genome AF: 0.0000133 AC: 2AN: 150300Hom.: 0 Cov.: 31 AF XY: 0.0000273 AC XY: 2AN XY: 73218
ClinVar
Submissions by phenotype
Ovarian cancer Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University | Jan 01, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 08, 2021 | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with bilateral retinoblastoma (He 2014); This variant is associated with the following publications: (PMID: 24791139) - |
Retinoblastoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 17, 2022 | 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