rs359955

chr1-32669173-A-Cchr1-32669173-A-T

Variant summary

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

The NM_005610.3(RBBP4):c.761+41A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 1,611,592 control chromosomes in the GnomAD database, including 466,787 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 0.63 (34004 hom., cov: 30)
  • Exomes 𝑓: 0.76 (432783 hom.)
• Consequence: RBBP4 NM_005610.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81

Genes affected

RBBP4 (HGNC:9887): (RB binding protein 4, chromatin remodeling factor) This gene encodes a ubiquitously expressed nuclear protein which belongs to a highly conserved subfamily of WD-repeat proteins. It is present in protein complexes involved in histone acetylation and chromatin assembly. It is part of the Mi-2 complex which has been implicated in chromatin remodeling and transcriptional repression associated with histone deacetylation. This encoded protein is also part of co-repressor complexes, which is an integral component of transcriptional silencing. It is found among several cellular proteins that bind directly to retinoblastoma protein to regulate cell proliferation. This protein also seems to be involved in transcriptional repression of E2F-responsive genes. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBBP4	NM_005610.3	c.761+41A>C		intron_variant		ENST00000373493.10
RBBP4	NM_001135255.2	c.758+41A>C		intron_variant
RBBP4	NM_001135256.2	c.656+41A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBBP4	ENST00000373493.10	c.761+41A>C		intron_variant		1	NM_005610.3	P3

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95661 AN: 151784 Hom.: 34003 Cov.: 30

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.620

GnomAD3 exomes AF: 0.733 AC: 182935 AN: 249642 Hom.: 69275 AF XY: 0.741 AC XY: 99944 AN XY: 134932

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.718

Gnomad ASJ exome AF: 0.689

Gnomad EAS exome AF: 0.731

Gnomad SAS exome AF: 0.736

Gnomad FIN exome AF: 0.848

Gnomad NFE exome AF: 0.786

Gnomad OTH exome AF: 0.732

GnomAD4 exome AF: 0.765 AC: 1115976 AN: 1459690 Hom.: 432783 Cov.: 55 AF XY: 0.765 AC XY: 555284 AN XY: 726036

Gnomad4 AFR exome AF: 0.253

Gnomad4 AMR exome AF: 0.709

Gnomad4 ASJ exome AF: 0.684

Gnomad4 EAS exome AF: 0.763

Gnomad4 SAS exome AF: 0.732

Gnomad4 FIN exome AF: 0.848

Gnomad4 NFE exome AF: 0.786

Gnomad4 OTH exome AF: 0.721

GnomAD4 genome AF: 0.630 AC: 95688 AN: 151902 Hom.: 34004 Cov.: 30 AF XY: 0.633 AC XY: 47027 AN XY: 74258

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.844

Gnomad4 NFE AF: 0.786

Gnomad4 OTH AF: 0.622

Alfa AF: 0.746 Hom.: 66557

Bravo AF: 0.597

Asia WGS AF: 0.710 AC: 2469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.0
Dann	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs359955; hg19: chr1-33134774; COSMIC: COSV65132650; COSMIC: COSV65132650;