1-32678295-T-C

Position:

• chr1-32678295-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBBP4	NM_005610.3	c.1213-1345T>C		intron_variant		ENST00000373493.10
RBBP4	NM_001135255.2	c.1210-1345T>C		intron_variant
RBBP4	NM_001135256.2	c.1108-1345T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBBP4	ENST00000373493.10	c.1213-1345T>C		intron_variant		1	NM_005610.3	P3

Frequencies

GnomAD3 genomes AF: 0.972 AC: 146515 AN: 150724 Hom.: 71337 Cov.: 31

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.: 31 AF XY: 0.973 AC XY: 71751 AN XY: 73750

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.987

Gnomad4 ASJ AF: 0.999

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.977

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.36
DANN	Benign	0.20

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

Other links and lift over

dbSNP: rs659867; hg19: chr1-33143896;