18-22946144-C-T
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_002894.3(RBBP8):c.110-300C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00611 in 152,320 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0061 ( 10 hom., cov: 32)
Consequence
RBBP8
NM_002894.3 intron
NM_002894.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.163
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 Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
Variant 18-22946144-C-T is Benign according to our data. Variant chr18-22946144-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1219069.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00611 (930/152320) while in subpopulation AFR AF= 0.0214 (891/41576). AF 95% confidence interval is 0.0203. There are 10 homozygotes in gnomad4. There are 438 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 10 AR gene
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| RBBP8 | NM_002894.3 | c.110-300C>T | intron_variant | ENST00000327155.10 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RBBP8 | ENST00000327155.10 | c.110-300C>T | intron_variant | 1 | NM_002894.3 | P1 |
Frequencies
GnomAD3 genomes 0.00608 AC: 925AN: 152202Hom.: 10 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.00611 AC: 930AN: 152320Hom.: 10 Cov.: 32 AF XY: 0.00588 AC XY: 438AN XY: 74472
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 20, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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