rs7243256

Positions:

• chr18-22936411-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002894.3(RBBP8):​c.-98-343C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 151,644 control chromosomes in the GnomAD database, including 35,810 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.68 (35810 hom., cov: 32)
• Consequence: RBBP8 NM_002894.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 18-22936411-C-A is Benign according to our data. Variant chr18-22936411-C-A is described in ClinVar as [Benign]. Clinvar id is 684037.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBBP8	NM_002894.3	c.-98-343C>A		intron_variant		ENST00000327155.10	NP_002885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBBP8	ENST00000327155.10	c.-98-343C>A		intron_variant		1	NM_002894.3	ENSP00000323050	P1

Frequencies

GnomAD3 genomes AF: 0.680 AC: 102967 AN: 151524 Hom.: 35796 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.679 AC: 103014 AN: 151644 Hom.: 35810 Cov.: 32 AF XY: 0.679 AC XY: 50327 AN XY: 74108

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.837

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.762

Gnomad4 OTH AF: 0.718

Alfa AF: 0.743 Hom.: 18765

Bravo AF: 0.664

Asia WGS AF: 0.579 AC: 2012 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.21
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: rs7243256; hg19: chr18-20516374;