Genetic Variant RBBP6:p.Gly168Gly (chr16-24555887-A-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_006910.5(RBBP6):c.504A>C(p.Gly168Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0064 in 1,607,360 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 27 hom. )

Consequence

RBBP6
NM_006910.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.02

Publications

5 publications found

Variant links:

Genes affected

RBBP6 (HGNC:9889): (RB binding protein 6, ubiquitin ligase) The retinoblastoma tumor suppressor (pRB) protein binds with many other proteins. In various human cancers, pRB suppresses cellular proliferation and is inactivated. Cell cycle-dependent phosphorylation regulates the activity of pRB. This gene encodes a protein which binds to underphosphorylated but not phosphorylated pRB. Multiple alternatively spliced transcript variants that encode different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RBBP6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 16-24555887-A-C is Benign according to our data. Variant chr16-24555887-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2443232.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.02 with no splicing effect.

BS2

High AC in GnomAd4 at 711 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBBP6	NM_006910.5 link	c.504A>C	p.Gly168Gly	synonymous_variant	Exon 6 of 18	ENST00000319715.10	NP_008841.2
RBBP6	NM_018703.4 link	c.504A>C	p.Gly168Gly	synonymous_variant	Exon 6 of 17		NP_061173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBBP6	ENST00000319715.10 link	c.504A>C	p.Gly168Gly	synonymous_variant	Exon 6 of 18	1	NM_006910.5	ENSP00000317872.4		Q7Z6E9-1

Frequencies

GnomAD3 genomes

AF:

0.00467

AC:

711

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00778

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00433

AC:

1087

AN:

251290

AF XY:

0.00445

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00379

Gnomad NFE exome

AF:

0.00796

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00658

AC:

9581

AN:

1455048

Hom.:

Cov.:

AF XY:

0.00624

AC XY:

4522

AN XY:

724366

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

33312

American (AMR)

AF:

0.00197

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0000767

AC:

AN:

26088

East Asian (EAS)

AF:

0.00

AC:

AN:

39660

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86120

European-Finnish (FIN)

AF:

0.00416

AC:

222

AN:

53402

Middle Eastern (MID)

AF:

0.000521

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00807

AC:

8921

AN:

1105820

Other (OTH)

AF:

0.00515

AC:

310

AN:

60182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

446

891

1337

1782

2228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00467

AC:

711

AN:

152312

Hom.:

Cov.:

AF XY:

0.00424

AC XY:

316

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00164

AC:

AN:

41572

American (AMR)

AF:

0.00314

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00339

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00778

AC:

529

AN:

68030

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00598

Hom.:

Bravo

AF:

0.00468

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00692

EpiControl

AF:

0.00729

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 21, 2022

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

RBBP6: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

-1.0

PromoterAI

0.048

Neutral

(source)

Mutation Taster

=92/8

polymorphism

(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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

16-24555887-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over