rs587776884
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1PP5
The NM_002894.3(RBBP8):c.1808_1809del(p.Ile603LysfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RBBP8
NM_002894.3 frameshift
NM_002894.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.979
Genes affected
RBBP8 (HGNC:9891): (RB binding protein 8, endonuclease) The protein encoded by this gene is a ubiquitously expressed nuclear protein. It is found among several proteins that bind directly to retinoblastoma protein, which regulates cell proliferation. This protein complexes with transcriptional co-repressor CTBP. It is also associated with BRCA1 and is thought to modulate the functions of BRCA1 in transcriptional regulation, DNA repair, and/or cell cycle checkpoint control. It is suggested that this gene may itself be a tumor suppressor acting in the same pathway as BRCA1. Three transcript variants encoding two different isoforms have been found for this gene. More transcript variants exist, but their full-length natures have not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 18-22993633-CAT-C is Pathogenic according to our data. Variant chr18-22993633-CAT-C is described in ClinVar as [Pathogenic]. Clinvar id is 30409.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBBP8 | NM_002894.3 | c.1808_1809del | p.Ile603LysfsTer7 | frameshift_variant | 11/19 | ENST00000327155.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBBP8 | ENST00000327155.10 | c.1808_1809del | p.Ile603LysfsTer7 | frameshift_variant | 11/19 | 1 | NM_002894.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1AN: 1461878Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727238
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
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1
AN:
1461878
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0
AN XY:
727238
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Jawad syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 2011 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at