chr13-48453063-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 4P and 10B. PM2PM5BP4_ModerateBP6_Very_Strong
The NM_000321.3(RB1):c.1766C>T(p.Ala589Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. A589G) has been classified as Likely benign.
Frequency
Consequence
NM_000321.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.1766C>T | p.Ala589Val | missense_variant | 18/27 | ENST00000267163.6 | |
RB1 | NM_001407165.1 | c.1766C>T | p.Ala589Val | missense_variant | 18/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.1766C>T | p.Ala589Val | missense_variant | 18/27 | 1 | NM_000321.3 | P1 | |
RB1 | ENST00000650461.1 | c.1766C>T | p.Ala589Val | missense_variant | 18/27 | ||||
RB1 | ENST00000643064.1 | c.194+71620C>T | intron_variant | ||||||
RB1 | ENST00000480491.1 | n.465C>T | non_coding_transcript_exon_variant | 2/3 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250962Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135684
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460960Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726808
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Retinoblastoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 22, 2022 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at