rs757747543
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_002894.3(RBBP8):βc.1223_1228delβ(p.Ile408_Asn409del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,612,764 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: π 0.000039 ( 0 hom., cov: 32)
Exomes π: 0.000026 ( 0 hom. )
Consequence
RBBP8
NM_002894.3 inframe_deletion
NM_002894.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.27
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 Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_002894.3.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBBP8 | NM_002894.3 | c.1223_1228del | p.Ile408_Asn409del | inframe_deletion | 11/19 | ENST00000327155.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBBP8 | ENST00000327155.10 | c.1223_1228del | p.Ile408_Asn409del | inframe_deletion | 11/19 | 1 | NM_002894.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000360 AC: 9AN: 249764Hom.: 0 AF XY: 0.0000590 AC XY: 8AN XY: 135602
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GnomAD4 exome AF: 0.0000260 AC: 38AN: 1460474Hom.: 0 AF XY: 0.0000303 AC XY: 22AN XY: 726596
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152290Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74448
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 07, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 03, 2022 | This variant, c.1223_1228del, results in the deletion of 2 amino acid(s) of the RBBP8 protein (p.Ile408_Asn409del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs757747543, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with RBBP8-related conditions. ClinVar contains an entry for this variant (Variation ID: 436511). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at