rs3738154

chr1-205094821-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005057.4(RBBP5):c.1588+52G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,540,704 control chromosomes in the GnomAD database, including 140,712 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 0.39 (12204 hom., cov: 31)
  • Exomes 𝑓: 0.42 (128508 hom.)
• Consequence: RBBP5 NM_005057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.573

Genes affected

RBBP5 (HGNC:9888): (RB binding protein 5, histone lysine methyltransferase complex subunit) This gene encodes a ubiquitously expressed nuclear protein which belongs to a highly conserved subfamily of WD-repeat proteins. The encoded protein binds directly to retinoblastoma protein, which regulates cell proliferation. It interacts preferentially with the underphosphorylated retinoblastoma protein via the E1A-binding pocket B. Three alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBBP5	NM_005057.4	c.1588+52G>A		intron_variant		ENST00000264515.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBBP5	ENST00000264515.11	c.1588+52G>A		intron_variant		1	NM_005057.4	P3
RBBP5	ENST00000367164.1	c.1474+166G>A		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59412 AN: 151852 Hom.: 12200 Cov.: 31

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.0936

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.421 AC: 585061 AN: 1388734 Hom.: 128508 Cov.: 25 AF XY: 0.417 AC XY: 286410 AN XY: 686674

Gnomad4 AFR exome AF: 0.352

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.473

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.247

Gnomad4 FIN exome AF: 0.511

Gnomad4 NFE exome AF: 0.449

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.391 AC: 59434 AN: 151970 Hom.: 12204 Cov.: 31 AF XY: 0.389 AC XY: 28879 AN XY: 74270

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.0940

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.382

Alfa AF: 0.424 Hom.: 20799

Bravo AF: 0.378

Asia WGS AF: 0.195 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	6.2
Dann	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3738154; hg19: chr1-205063949; COSMIC: COSV52707628; COSMIC: COSV52707628;