rs759465865
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_000321.3(RB1):c.34_42del(p.Thr12_Ala14del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000184 in 1,357,732 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A10A) has been classified as Likely benign.
Frequency
Consequence
NM_000321.3 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.34_42del | p.Thr12_Ala14del | inframe_deletion | 1/27 | ENST00000267163.6 | |
RB1 | NM_001407165.1 | c.34_42del | p.Thr12_Ala14del | inframe_deletion | 1/27 | ||
RB1 | NM_001407166.1 | c.34_42del | p.Thr12_Ala14del | inframe_deletion | 1/17 | ||
RB1 | NM_001407167.1 | c.34_42del | p.Thr12_Ala14del | inframe_deletion | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.34_42del | p.Thr12_Ala14del | inframe_deletion | 1/27 | 1 | NM_000321.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000761 AC: 8AN: 105152Hom.: 0 AF XY: 0.0000681 AC XY: 4AN XY: 58734
GnomAD4 exome AF: 0.0000184 AC: 25AN: 1357732Hom.: 0 AF XY: 0.0000164 AC XY: 11AN XY: 669812
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Retinoblastoma Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 14, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jun 26, 2023 | This variant is a 3 amino acid deletion located at positions 12-14 in the RB1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RB1-related disorders in the literature. This variant has been identified in 8/105152 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 13, 2021 | 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