18-22914589-T-C

Position:

• chr18-22914589-T-C

Variant summary

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

The ENST00000579124.5(RBBP8):​c.-165+283T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,112 control chromosomes in the GnomAD database, including 21,286 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 (21286 hom., cov: 32)
• Consequence: RBBP8 ENST00000579124.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.976

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]

ENSG00000265943 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• 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	Protein	UniProt
RBBP8	XM_006722519.3	c.-220+283T>C		intron_variant			XP_006722582.1
RBBP8	XM_006722520.3	c.-154+283T>C		intron_variant			XP_006722583.1
RBBP8	XM_011526132.3	c.-165+283T>C		intron_variant			XP_011524434.1
RBBP8	XM_047437728.1	c.-325+283T>C		intron_variant			XP_047293684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBBP8	ENST00000582354.5	c.-220+283T>C		intron_variant		5		ENSP00000463738.1
RBBP8	ENST00000581819.5	c.-154+283T>C		intron_variant		5		ENSP00000463439.1
RBBP8	ENST00000579124.5	c.-165+283T>C		intron_variant		4		ENSP00000462390.1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73962 AN: 151994 Hom.: 21294 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.486 AC: 73944 AN: 152112 Hom.: 21286 Cov.: 32 AF XY: 0.486 AC XY: 36156 AN XY: 74362

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.556

Alfa AF: 0.616 Hom.: 60501

Bravo AF: 0.468

Asia WGS AF: 0.478 AC: 1660 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1379805; hg19: chr18-20494552;