Genetic Variant RBBP6:c.348+15_348+18dupATAT (chr16-24553558-G-GTATA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006910.5(RBBP6):c.348+15_348+18dupATAT variant causes a intron change. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

RBBP6
NM_006910.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBBP6	NM_006910.5 link	c.348+15_348+18dupATAT		intron_variant	Intron 4 of 17	ENST00000319715.10	NP_008841.2
RBBP6	NM_018703.4 link	c.348+15_348+18dupATAT		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+15_348+18dupATAT		intron_variant	Intron 4 of 17	1	NM_006910.5	ENSP00000317872.4		Q7Z6E9-1

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149780

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000298

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000579

AC:

AN:

172582

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000239

GnomAD4 exome

AF:

0.0000495

AC:

AN:

1292222

Hom.:

Cov.:

AF XY:

0.0000512

AC XY:

AN XY:

644728

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

26890

American (AMR)

AF:

0.00

AC:

AN:

37670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23042

East Asian (EAS)

AF:

0.0000267

AC:

AN:

37466

South Asian (SAS)

AF:

0.00

AC:

AN:

70868

European-Finnish (FIN)

AF:

0.0000209

AC:

AN:

47924

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4034

European-Non Finnish (NFE)

AF:

0.0000605

AC:

AN:

991138

Other (OTH)

AF:

0.0000376

AC:

AN:

53190

⚠️ 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: 0.345

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000134

AC:

AN:

149780

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73038

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40894

American (AMR)

AF:

0.00

AC:

AN:

14994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

5132

South Asian (SAS)

AF:

0.00

AC:

AN:

4778

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10170

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000298

AC:

AN:

67106

Other (OTH)

AF:

0.00

AC:

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

1776

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.9

Splicing

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

Publications

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16-24553558-GTATATA-GTATATATATA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over