rs4474794

chr18-22987010-C-Achr18-22987010-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002894.3(RBBP8):c.709+2020C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 152,064 control chromosomes in the GnomAD database, including 21,359 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (21359 hom., cov: 32)
• Consequence: RBBP8 NM_002894.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBBP8	NM_002894.3	c.709+2020C>A		intron_variant		ENST00000327155.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBBP8	ENST00000327155.10	c.709+2020C>A		intron_variant		1	NM_002894.3	P1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74135 AN: 151946 Hom.: 21361 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.557

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.487 AC: 74129 AN: 152064 Hom.: 21359 Cov.: 32 AF XY: 0.489 AC XY: 36327 AN XY: 74326

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.554

Alfa AF: 0.578 Hom.: 12265

Bravo AF: 0.468

Asia WGS AF: 0.484 AC: 1683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.3
Dann	Benign	0.38

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: rs4474794; hg19: chr18-20566973;