1-32668367-T-G

Variant names:

• chr1-32668367-T-G
• rs2762904
• NM_005610.3:c.453T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP7

The NM_005610.3(RBBP4):​c.453T>G​(p.Val151Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V151V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RBBP4 NM_005610.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 19 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP7: Synonymous conserved (PhyloP=-0.113 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBBP4	NM_005610.3	MANE Select	c.453T>G	p.Val151Val	synonymous	Exon 4 of 12	NP_005601.1	Q09028-1
	RBBP4	NM_001135255.2		c.450T>G	p.Val150Val	synonymous	Exon 4 of 12	NP_001128727.1	Q09028-2
	RBBP4	NM_001135256.2		c.348T>G	p.Val116Val	synonymous	Exon 4 of 12	NP_001128728.1	Q09028-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBBP4	ENST00000373493.10	TSL:1 MANE Select	c.453T>G	p.Val151Val	synonymous	Exon 4 of 12	ENSP00000362592.4	Q09028-1
	RBBP4	ENST00000414241.7	TSL:1	c.450T>G	p.Val150Val	synonymous	Exon 4 of 12	ENSP00000398242.3	Q09028-2
	RBBP4	ENST00000373485.5	TSL:1	c.453T>G	p.Val151Val	synonymous	Exon 4 of 12	ENSP00000362584.1	Q09028-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	5.6
DANN	Benign	0.66
PhyloP100		-0.11
PromoterAI		0.0079	Neutral
Mutation Taster		=93/7	polymorphism

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: rs2762904; hg19: chr1-33133968;