Genetic Variant RBBP6:c.348+17_348+18dupAT (chr16-24553558-G-GTA) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The NM_006910.5(RBBP6):c.348+17_348+18dupAT variant causes a intron change. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0017 ( 0 hom. )

Consequence

RBBP6
NM_006910.5 intron

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.87

Publications

7 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP6

Variant 16-24553558-G-GTA is Benign according to our data. Variant chr16-24553558-G-GTA is described in ClinVar as [Likely_benign]. Clinvar id is 2443233.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 85 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBBP6	NM_006910.5 link	c.348+17_348+18dupAT		intron_variant	Intron 4 of 17	ENST00000319715.10	NP_008841.2
RBBP6	NM_018703.4 link	c.348+17_348+18dupAT		intron_variant	Intron 4 of 16		NP_061173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBBP6	ENST00000319715.10 link	c.348+17_348+18dupAT		intron_variant	Intron 4 of 17	1	NM_006910.5	ENSP00000317872.4		Q7Z6E9-1

Frequencies

GnomAD3 genomes

AF:

0.000568

AC:

AN:

149770

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000534

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000779

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.0000984

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000894

Gnomad OTH

AF:

0.00146

GnomAD2 exomes

AF:

0.000944

AC:

163

AN:

172582

AF XY:

0.000948

show subpopulations

Gnomad AFR exome

AF:

0.000107

Gnomad AMR exome

AF:

0.00111

Gnomad ASJ exome

AF:

0.000597

Gnomad EAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.000858

Gnomad NFE exome

AF:

0.00102

Gnomad OTH exome

AF:

0.000239

GnomAD4 exome

AF:

0.00166

AC:

2136

AN:

1283108

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1046

AN XY:

640428

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000372

AC:

AN:

26866

American (AMR)

AF:

0.000931

AC:

AN:

37584

Ashkenazi Jewish (ASJ)

AF:

0.000785

AC:

AN:

22934

East Asian (EAS)

AF:

0.000940

AC:

AN:

37238

South Asian (SAS)

AF:

0.000693

AC:

AN:

70710

European-Finnish (FIN)

AF:

0.000545

AC:

AN:

47734

Middle Eastern (MID)

AF:

0.000746

AC:

AN:

4022

European-Non Finnish (NFE)

AF:

0.00193

AC:

1900

AN:

983128

Other (OTH)

AF:

0.00113

AC:

AN:

52892

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.290

Heterozygous variant carriers

222

444

667

889

1111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000567

AC:

AN:

149890

Hom.:

Cov.:

AF XY:

0.000492

AC XY:

AN XY:

73164

show subpopulations

African (AFR)

AF:

0.000195

AC:

AN:

41016

American (AMR)

AF:

0.000533

AC:

AN:

15014

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3438

East Asian (EAS)

AF:

0.000781

AC:

AN:

5122

South Asian (SAS)

AF:

0.000210

AC:

AN:

4772

European-Finnish (FIN)

AF:

0.0000984

AC:

AN:

10164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000894

AC:

AN:

67094

Other (OTH)

AF:

0.00145

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00275

Hom.:

1776

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 16, 2022

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.9

Mutation Taster

=30/70

disease causing

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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16-24553558-G-GTA

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