NM_005610.3:c.1212+14A>C

Variant names:

• chr1-32672915-A-C
• rs607202
• NM_005610.3:c.1212+14A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.502
• Publications: 7 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 -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 VariationId 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.

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.1212+14A>C		intron	N/A	NP_005601.1	Q09028-1
	RBBP4	NM_001135255.2		c.1209+14A>C		intron	N/A	NP_001128727.1	Q09028-2
	RBBP4	NM_001135256.2		c.1107+14A>C		intron	N/A	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.1212+14A>C		intron	N/A	ENSP00000362592.4	Q09028-1
	RBBP4	ENST00000414241.7	TSL:1	c.1209+14A>C		intron	N/A	ENSP00000398242.3	Q09028-2
	RBBP4	ENST00000373485.5	TSL:1	c.1212+14A>C		intron	N/A	ENSP00000362584.1	Q09028-3

Frequencies

GnomAD3 genomes AF: 0.973 AC: 148060 AN: 152134 Hom.: 72174 Cov.: 32

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

GnomAD2 exomes AF: 0.993 AC: 248172 AN: 249926 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 AF: 0.997 AC: 1421908 AN: 1425628 Hom.: 709243 Cov.: 29 AF XY: 0.998 AC XY: 709090 AN XY: 710718

African (AFR) AF: 0.911 AC: 29638 AN: 32544

American (AMR) AF: 0.994 AC: 44253 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 25905 AN: 25920

East Asian (EAS) AF: 1.00 AC: 39459 AN: 39460

South Asian (SAS) AF: 1.00 AC: 85269 AN: 85280

European-Finnish (FIN) AF: 1.00 AC: 53357 AN: 53358

Middle Eastern (MID) AF: 0.998 AC: 4438 AN: 4446

European-Non Finnish (NFE) AF: 1.00 AC: 1080911 AN: 1081060

Other (OTH) AF: 0.994 AC: 58678 AN: 59058

GnomAD4 genome AF: 0.973 AC: 148173 AN: 152252 Hom.: 72230 Cov.: 32 AF XY: 0.974 AC XY: 72506 AN XY: 74444

African (AFR) AF: 0.908 AC: 37684 AN: 41512

American (AMR) AF: 0.988 AC: 15102 AN: 15288

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

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5186

South Asian (SAS) AF: 1.00 AC: 4814 AN: 4814

European-Finnish (FIN) AF: 1.00 AC: 10620 AN: 10620

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

European-Non Finnish (NFE) AF: 1.00 AC: 68022 AN: 68038

Other (OTH) AF: 0.979 AC: 2071 AN: 2116

Alfa AF: 0.986 Hom.: 24948

Bravo AF: 0.969

Asia WGS AF: 0.996 AC: 3465 AN: 3478

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	-0.89
CADD	Benign	1.6
DANN	Benign	0.44
PhyloP100		-0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs607202; hg19: chr1-33138516;