Genetic Variant RBBP4:c.1213-1345T>C (chr1-32678295-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005610.3(RBBP4):c.1213-1345T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.972 in 150,846 control chromosomes in the GnomAD database, including 71,394 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 0.97 ( 71394 hom., cov: 31)

Consequence

RBBP4
NM_005610.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.60

Publications

1 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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new If you want to explore the variant's impact on the transcript NM_005610.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RBBP4	NM_005610.3	MANE Select	c.1213-1345T>C	intron	N/A	NP_005601.1	Q09028-1
RBBP4	NM_001135255.2		c.1210-1345T>C	intron	N/A	NP_001128727.1	Q09028-2
RBBP4	NM_001135256.2		c.1108-1345T>C	intron	N/A	NP_001128728.1	Q09028-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RBBP4	ENST00000373493.10	TSL:1 MANE Select	c.1213-1345T>C	intron	N/A	ENSP00000362592.4	Q09028-1
RBBP4	ENST00000414241.7	TSL:1	c.1210-1345T>C	intron	N/A	ENSP00000398242.3	Q09028-2
RBBP4	ENST00000373485.5	TSL:1	c.1213-2231T>C	intron	N/A	ENSP00000362584.1	Q09028-3

Frequencies

GnomAD3 genomes

AF:

0.972

AC:

146515

AN:

150724

Hom.:

71337

Cov.:

show subpopulations

Gnomad AFR

AF:

0.906

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.987

Gnomad ASJ

AF:

0.999

Gnomad EAS

AF:

0.996

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

0.999

Gnomad MID

AF:

0.987

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.977

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.972

AC:

146631

AN:

150846

Hom.:

71394

Cov.:

AF XY:

0.973

AC XY:

71751

AN XY:

73750

show subpopulations

African (AFR)

AF:

0.906

AC:

37284

AN:

41150

American (AMR)

AF:

0.987

AC:

14941

AN:

15138

Ashkenazi Jewish (ASJ)

AF:

0.999

AC:

3430

AN:

3434

East Asian (EAS)

AF:

0.996

AC:

5062

AN:

5080

South Asian (SAS)

AF:

0.999

AC:

4753

AN:

4760

European-Finnish (FIN)

AF:

0.999

AC:

10539

AN:

10548

Middle Eastern (MID)

AF:

0.986

AC:

274

AN:

278

European-Non Finnish (NFE)

AF:

0.999

AC:

67423

AN:

67486

Other (OTH)

AF:

0.977

AC:

2021

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

182

364

547

729

911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.985

Hom.:

8606

Bravo

AF:

0.968

Asia WGS

AF:

0.990

AC:

3441

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.36

(source)

DANN

Benign

0.20

PhyloP100

-2.6

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over