NM_005610.3:c.761+41A>C

Variant names:

• chr1-32669173-A-C
• rs359955
• NM_005610.3:c.761+41A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005610.3. 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
	RBBP4	NM_005610.3	MANE Select	c.761+41A>C		intron	N/A	NP_005601.1
	RBBP4	NM_001135255.2		c.758+41A>C		intron	N/A	NP_001128727.1
	RBBP4	NM_001135256.2		c.656+41A>C		intron	N/A	NP_001128728.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBBP4	ENST00000373493.10	TSL:1 MANE Select	c.761+41A>C		intron	N/A	ENSP00000362592.4
	RBBP4	ENST00000414241.7	TSL:1	c.758+41A>C		intron	N/A	ENSP00000398242.3
	RBBP4	ENST00000373485.5	TSL:1	c.761+41A>C		intron	N/A	ENSP00000362584.1

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

GnomAD2 exomes AF: 0.733 AC: 182935 AN: 249642 AF XY: 0.741

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 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

African (AFR) AF: 0.253 AC: 8402 AN: 33252

American (AMR) AF: 0.709 AC: 31379 AN: 44258

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 17825 AN: 26076

East Asian (EAS) AF: 0.763 AC: 30270 AN: 39686

South Asian (SAS) AF: 0.732 AC: 62840 AN: 85802

European-Finnish (FIN) AF: 0.848 AC: 45294 AN: 53408

Middle Eastern (MID) AF: 0.573 AC: 3300 AN: 5756

European-Non Finnish (NFE) AF: 0.786 AC: 873218 AN: 1111178

Other (OTH) AF: 0.721 AC: 43448 AN: 60274

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

African (AFR) AF: 0.275 AC: 11379 AN: 41388

American (AMR) AF: 0.651 AC: 9917 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2365 AN: 3464

East Asian (EAS) AF: 0.744 AC: 3831 AN: 5146

South Asian (SAS) AF: 0.749 AC: 3611 AN: 4824

European-Finnish (FIN) AF: 0.844 AC: 8903 AN: 10554

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.786 AC: 53418 AN: 67976

Other (OTH) AF: 0.622 AC: 1311 AN: 2108

Alfa AF: 0.729 Hom.: 164377

Bravo AF: 0.597

Asia WGS AF: 0.710 AC: 2469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.0
DANN	Benign	0.52
PhyloP100		2.8
PromoterAI		0.038	Neutral
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)		0.010		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: rs359955; hg19: chr1-33134774; COSMIC: COSV65132650; COSMIC: COSV65132650;