Genetic Variant RBBP4:p.Ala2Ser (chr1-32651310-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005610.3(RBBP4):c.4G>T(p.Ala2Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RBBP4
NM_005610.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.77

Publications

0 publications found

Variant links:

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]

RBBP4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28700104).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBBP4	NM_005610.3	MANE Select	c.4G>T	p.Ala2Ser	missense	Exon 1 of 12	NP_005601.1	Q09028-1
RBBP4	NM_001135255.2		c.4G>T	p.Ala2Ser	missense	Exon 1 of 12	NP_001128727.1	Q09028-2
RBBP4	NM_001135256.2		c.-212G>T		upstream_gene	N/A	NP_001128728.1	Q09028-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBBP4	ENST00000373493.10	TSL:1 MANE Select	c.4G>T	p.Ala2Ser	missense	Exon 1 of 12	ENSP00000362592.4	Q09028-1
RBBP4	ENST00000414241.7	TSL:1	c.4G>T	p.Ala2Ser	missense	Exon 1 of 12	ENSP00000398242.3	Q09028-2
RBBP4	ENST00000373485.5	TSL:1	c.4G>T	p.Ala2Ser	missense	Exon 1 of 12	ENSP00000362584.1	Q09028-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1319938

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

647536

African (AFR)

AF:

0.00

AC:

AN:

26112

American (AMR)

AF:

0.00

AC:

AN:

23580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20350

East Asian (EAS)

AF:

0.00

AC:

AN:

30500

South Asian (SAS)

AF:

0.00

AC:

AN:

69944

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46084

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4626

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1044420

Other (OTH)

AF:

0.00

AC:

AN:

54322

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

0.0064

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.088

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.061

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.8

PhyloP100

3.8

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.32

REVEL

Benign

0.087

Sift

Benign

0.045

Sift4G

Benign

0.22

Polyphen

0.0

Vest4

0.30

MutPred

0.25

Gain of phosphorylation at A2 (P = 0.0102)

MVP

0.75

MPC

1.5

ClinPred

0.85

GERP RS

4.0

PromoterAI

-0.077

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.38

gMVP

0.62

Mutation Taster

=78/22

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over