1-32668367-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BA1

The NM_005610.3(RBBP4):​c.453T>C​(p.Val151Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.973 in 152,258 control chromosomes in the GnomAD database, including 72,233 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (72233 hom., cov: 31)
  • Exomes 𝑓: 1.0 (724249 hom.)
  • Failed GnomAD Quality Control
• Consequence: RBBP4 NM_005610.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -17 ACMG points.

• BP6: Variant 1-32668367-T-C is Benign according to our data. Variant chr1-32668367-T-C is described in ClinVar as Benign. ClinVar VariationId is 1263039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.113 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBBP4	NM_005610.3	MANE Select	c.453T>C	p.Val151Val	synonymous	Exon 4 of 12	NP_005601.1	Q09028-1
	RBBP4	NM_001135255.2		c.450T>C	p.Val150Val	synonymous	Exon 4 of 12	NP_001128727.1	Q09028-2
	RBBP4	NM_001135256.2		c.348T>C	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>C	p.Val151Val	synonymous	Exon 4 of 12	ENSP00000362592.4	Q09028-1
	RBBP4	ENST00000414241.7	TSL:1	c.450T>C	p.Val150Val	synonymous	Exon 4 of 12	ENSP00000398242.3	Q09028-2
	RBBP4	ENST00000373485.5	TSL:1	c.453T>C	p.Val151Val	synonymous	Exon 4 of 12	ENSP00000362584.1	Q09028-3

Frequencies

GnomAD3 genomes AF: 0.973 AC: 148069 AN: 152140 Hom.: 72177 Cov.: 31

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: 0.978

GnomAD2 exomes AF: 0.993 AC: 249481 AN: 251256 AF XY: 0.995

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 FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.993

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.997 AC: 1452004 AN: 1455818 Hom.: 724249 Cov.: 51 AF XY: 0.998 AC XY: 723029 AN XY: 724690

African (AFR) AF: 0.910 AC: 30365 AN: 33366

American (AMR) AF: 0.994 AC: 44448 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 26073 AN: 26088

East Asian (EAS) AF: 1.00 AC: 39658 AN: 39658

South Asian (SAS) AF: 1.00 AC: 86093 AN: 86102

European-Finnish (FIN) AF: 1.00 AC: 53420 AN: 53420

Middle Eastern (MID) AF: 0.998 AC: 5745 AN: 5756

European-Non Finnish (NFE) AF: 1.00 AC: 1106384 AN: 1106528

Other (OTH) AF: 0.994 AC: 59818 AN: 60202

GnomAD4 genome AF: 0.973 AC: 148182 AN: 152258 Hom.: 72233 Cov.: 31 AF XY: 0.974 AC XY: 72509 AN XY: 74446

African (AFR) AF: 0.908 AC: 37701 AN: 41524

American (AMR) AF: 0.988 AC: 15086 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3470 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5188 AN: 5188

South Asian (SAS) AF: 1.00 AC: 4824 AN: 4824

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10618

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68024 AN: 68040

Other (OTH) AF: 0.979 AC: 2067 AN: 2112

Alfa AF: 0.986 Hom.: 33849

Bravo AF: 0.969

Asia WGS AF: 0.997 AC: 3465 AN: 3476

EpiCase AF: 1.00

EpiControl AF: 1.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.0
DANN	Benign	0.68
PhyloP100		-0.11
PromoterAI		0.017	Neutral
Mutation Taster		=93/7	polymorphism (auto)

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; COSMIC: COSV108221579; COSMIC: COSV108221579;