rs7234479

Positions:

• chr18-23019601-A-C
• chr18-23019601-A-G

Variant summary

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

The NM_002894.3(RBBP8):​c.2455-2528A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,000 control chromosomes in the GnomAD database, including 3,096 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 0.17 (3096 hom., cov: 32)
• Consequence: RBBP8 NM_002894.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.06

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBBP8	NM_002894.3	c.2455-2528A>C		intron_variant		ENST00000327155.10	NP_002885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBBP8	ENST00000327155.10	c.2455-2528A>C		intron_variant		1	NM_002894.3	ENSP00000323050	P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26381 AN: 151882 Hom.: 3096 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0948

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.0948

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.174 AC: 26406 AN: 152000 Hom.: 3096 Cov.: 32 AF XY: 0.171 AC XY: 12730 AN XY: 74298

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.0945

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.0948

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.156

Alfa AF: 0.115 Hom.: 550

Bravo AF: 0.179

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0030
DANN	Benign	0.81

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: rs7234479; hg19: chr18-20599564;