Variant 1-32672915-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005610.3(RBBP4):c.1212+14A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,577,880 control chromosomes in the GnomAD database, including 781,473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 72230 hom., cov: 32)

Exomes 𝑓: 1.0 ( 709243 hom. )

Consequence

RBBP4
NM_005610.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.502

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-32672915-A-C is Benign according to our data. Variant chr1-32672915-A-C is described in ClinVar as [Benign]. Clinvar id is 1272785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
RBBP4	NM_005610.3 linkuse as main transcript	c.1212+14A>C	intron_variant	ENST00000373493.10	NP_005601.1	Q09028-1
RBBP4	NM_001135255.2 linkuse as main transcript	c.1209+14A>C	intron_variant		NP_001128727.1	Q09028-2
RBBP4	NM_001135256.2 linkuse as main transcript	c.1107+14A>C	intron_variant		NP_001128728.1	Q09028-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBBP4	ENST00000373493.10 linkuse as main transcript	c.1212+14A>C		intron_variant		1	NM_005610.3	ENSP00000362592.4		Q09028-1
RBBP4	ENST00000482190.1 linkuse as main transcript	c.426+14A>C		intron_variant		3		ENSP00000436565.1		H0YEU5

Frequencies

GnomAD3 genomes

AF:

0.973

AC:

148060

AN:

152134

Hom.:

72174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.908

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.988

Gnomad ASJ

AF:

0.999

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.979

GnomAD3 exomes

AF:

0.993

AC:

248172

AN:

249926

Hom.:

123282

AF XY:

0.995

AC XY:

134531

AN XY:

135222

show subpopulations

Gnomad AFR exome

AF:

0.906

Gnomad AMR exome

AF:

0.995

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.993

GnomAD4 exome

AF:

0.997

AC:

1421908

AN:

1425628

Hom.:

709243

Cov.:

AF XY:

0.998

AC XY:

709090

AN XY:

710718

show subpopulations

Gnomad4 AFR exome

AF:

0.911

Gnomad4 AMR exome

AF:

0.994

Gnomad4 ASJ exome

AF:

0.999

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.994

GnomAD4 genome

AF:

0.973

AC:

148173

AN:

152252

Hom.:

72230

Cov.:

AF XY:

0.974

AC XY:

72506

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.908

Gnomad4 AMR

AF:

0.988

Gnomad4 ASJ

AF:

0.999

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.979

Alfa

AF:

0.985

Hom.:

14291

Bravo

AF:

0.969

Asia WGS

AF:

0.996

AC:

3465

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 30, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.6

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over