chr18-22946270-CA-C

Position:

• chr18-22946270-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002894.3(RBBP8):​c.110-172del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 722,814 control chromosomes in the GnomAD database, including 371 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (86 hom., cov: 32)
  • Exomes 𝑓: 0.023 (285 hom.)
• Consequence: RBBP8 NM_002894.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.35

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 18-22946270-CA-C is Benign according to our data. Variant chr18-22946270-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1205082.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBBP8	NM_002894.3	c.110-172del		intron_variant		ENST00000327155.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBBP8	ENST00000327155.10	c.110-172del		intron_variant		1	NM_002894.3	P1

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4144 AN: 152058 Hom.: 88 Cov.: 32

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0233

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.0826

Gnomad SAS AF: 0.0619

Gnomad FIN AF: 0.00549

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0368

GnomAD4 exome AF: 0.0228 AC: 12997 AN: 570638 Hom.: 285 AF XY: 0.0243 AC XY: 7129 AN XY: 293240

Gnomad4 AFR exome AF: 0.0500

Gnomad4 AMR exome AF: 0.0172

Gnomad4 ASJ exome AF: 0.0278

Gnomad4 EAS exome AF: 0.0554

Gnomad4 SAS exome AF: 0.0572

Gnomad4 FIN exome AF: 0.00525

Gnomad4 NFE exome AF: 0.0158

Gnomad4 OTH exome AF: 0.0317

GnomAD4 genome AF: 0.0273 AC: 4147 AN: 152176 Hom.: 86 Cov.: 32 AF XY: 0.0272 AC XY: 2023 AN XY: 74394

Gnomad4 AFR AF: 0.0431

Gnomad4 AMR AF: 0.0233

Gnomad4 ASJ AF: 0.0254

Gnomad4 EAS AF: 0.0824

Gnomad4 SAS AF: 0.0615

Gnomad4 FIN AF: 0.00549

Gnomad4 NFE AF: 0.0153

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0194 Hom.: 8

Bravo AF: 0.0302

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 26, 2020

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs148996166; hg19: chr18-20526233;