chr16-24553558-GTATA-G

Variant names:

• chr16-24553558-GTATA-G
• rs72133882
• NM_006910.5:c.348+15_348+18delATAT

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+18delATAT variant causes a intron change. The variant allele was found at a frequency of 0.00601 in 1,361,558 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000067 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0067 (0 hom.)
• Consequence: RBBP6 NM_006910.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.83
• Publications: 7 publications found

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]

ACMG classification

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	c.348+15_348+18delATAT		intron_variant	Intron 4 of 17	ENST00000319715.10	NP_008841.2
RBBP6	NM_018703.4	c.348+15_348+18delATAT		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	c.348+15_348+18delATAT		intron_variant	Intron 4 of 17	1	NM_006910.5	ENSP00000317872.4

Frequencies

GnomAD3 genomes AF: 0.00000668 AC: 1 AN: 149712 Hom.: 0 Cov.: 0

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: 0.0000149

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0131 AC: 2254 AN: 172582 AF XY: 0.0124

Gnomad AFR exome AF: 0.0330

Gnomad AMR exome AF: 0.0135

Gnomad ASJ exome AF: 0.00971

Gnomad EAS exome AF: 0.00856

Gnomad FIN exome AF: 0.0117

Gnomad NFE exome AF: 0.0105

Gnomad OTH exome AF: 0.0112

GnomAD4 exome AF: 0.00675 AC: 8179 AN: 1211728 Hom.: 0 AF XY: 0.00702 AC XY: 4224 AN XY: 601816

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

African (AFR) AF: 0.0208 AC: 475 AN: 22788

American (AMR) AF: 0.0108 AC: 362 AN: 33580

Ashkenazi Jewish (ASJ) AF: 0.00787 AC: 164 AN: 20840

East Asian (EAS) AF: 0.00482 AC: 172 AN: 35672

South Asian (SAS) AF: 0.0159 AC: 973 AN: 61294

European-Finnish (FIN) AF: 0.00799 AC: 354 AN: 44316

Middle Eastern (MID) AF: 0.0105 AC: 39 AN: 3710

European-Non Finnish (NFE) AF: 0.00560 AC: 5265 AN: 940164

Other (OTH) AF: 0.00760 AC: 375 AN: 49364

⚠️ 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.

GnomAD4 genome AF: 0.00000667 AC: 1 AN: 149830 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 73130

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

African (AFR) AF: 0.00 AC: 0 AN: 41004

American (AMR) AF: 0.00 AC: 0 AN: 15010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3434

East Asian (EAS) AF: 0.00 AC: 0 AN: 5120

South Asian (SAS) AF: 0.00 AC: 0 AN: 4772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67068

Other (OTH) AF: 0.00 AC: 0 AN: 2076

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0270 Hom.: 1776

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.8
Mutation Taster		=87/13	polymorphism

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: rs72133882; hg19: chr16-24564879;