ENST00000582354.5:c.-220+283T>C

Variant names:

• chr18-22914589-T-C
• rs1379805
• ENST00000582354.5:c.-220+283T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000582354.5(RBBP8):​c.-220+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 ENST00000582354.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.976
• Publications: 5 publications found

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]

RBBP8 Gene-Disease associations (from GenCC):

• Jawad syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• Seckel syndrome 2

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• Seckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000266850 (HGNC:58091):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000582354.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBBP8-AS1	NR_198963.1		n.287+6173A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBBP8	ENST00000582354.5	TSL:5	c.-220+283T>C		intron	N/A	ENSP00000463738.1
	RBBP8	ENST00000581819.5	TSL:5	c.-154+283T>C		intron	N/A	ENSP00000463439.1
	RBBP8	ENST00000579124.5	TSL:4	c.-165+283T>C		intron	N/A	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

African (AFR) AF: 0.159 AC: 6617 AN: 41526

American (AMR) AF: 0.559 AC: 8549 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2384 AN: 3468

East Asian (EAS) AF: 0.453 AC: 2342 AN: 5172

South Asian (SAS) AF: 0.539 AC: 2601 AN: 4826

European-Finnish (FIN) AF: 0.591 AC: 6241 AN: 10562

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43369 AN: 67964

Other (OTH) AF: 0.556 AC: 1174 AN: 2110

Alfa AF: 0.598 Hom.: 76335

Bravo AF: 0.468

Asia WGS AF: 0.478 AC: 1660 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		0.98
PromoterAI		-0.012	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1379805; hg19: chr18-20494552;