chr1-205094821-C-T

Variant names:

• chr1-205094821-C-T
• rs3738154
• NM_005057.4:c.1588+52G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

RBBP5 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005057.4. 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
	RBBP5	NM_005057.4	MANE Select	c.1588+52G>A		intron	N/A	NP_005048.2
	RBBP5	NM_001193272.2		c.1474+166G>A		intron	N/A	NP_001180201.1
	RBBP5	NM_001193273.2		c.1207+52G>A		intron	N/A	NP_001180202.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBBP5	ENST00000264515.11	TSL:1 MANE Select	c.1588+52G>A		intron	N/A	ENSP00000264515.6
	RBBP5	ENST00000367164.1	TSL:1	c.1474+166G>A		intron	N/A	ENSP00000356132.1
	RBBP5	ENST00000861178.1		c.1588+52G>A		intron	N/A	ENSP00000531237.1

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

African (AFR) AF: 0.352 AC: 11020 AN: 31316

American (AMR) AF: 0.266 AC: 10025 AN: 37710

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 10838 AN: 22930

East Asian (EAS) AF: 0.104 AC: 3987 AN: 38262

South Asian (SAS) AF: 0.247 AC: 18969 AN: 76910

European-Finnish (FIN) AF: 0.511 AC: 26385 AN: 51590

Middle Eastern (MID) AF: 0.328 AC: 1568 AN: 4786

European-Non Finnish (NFE) AF: 0.449 AC: 479354 AN: 1067988

Other (OTH) AF: 0.400 AC: 22915 AN: 57242

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

African (AFR) AF: 0.359 AC: 14882 AN: 41452

American (AMR) AF: 0.320 AC: 4882 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1629 AN: 3466

East Asian (EAS) AF: 0.0940 AC: 486 AN: 5172

South Asian (SAS) AF: 0.238 AC: 1149 AN: 4820

European-Finnish (FIN) AF: 0.517 AC: 5443 AN: 10528

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29753 AN: 67948

Other (OTH) AF: 0.382 AC: 808 AN: 2114

Alfa AF: 0.418 Hom.: 29960

Bravo AF: 0.378

Asia WGS AF: 0.195 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.2
DANN	Benign	0.73
PhyloP100		-0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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