rs2033214

Positions:

• chr16-24566199-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006910.5(RBBP6):​c.1590-944T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,210 control chromosomes in the GnomAD database, including 1,936 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1936 hom., cov: 32)
• Consequence: RBBP6 NM_006910.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBBP6	NM_006910.5	c.1590-944T>G		intron_variant		ENST00000319715.10	NP_008841.2
RBBP6	NM_018703.4	c.1590-944T>G		intron_variant			NP_061173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBBP6	ENST00000319715.10	c.1590-944T>G		intron_variant		1	NM_006910.5	ENSP00000317872	P3

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21975 AN: 152092 Hom.: 1930 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0953

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.133

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.144 AC: 21991 AN: 152210 Hom.: 1936 Cov.: 32 AF XY: 0.147 AC XY: 10928 AN XY: 74430

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.0951

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.132

Alfa AF: 0.122 Hom.: 807

Bravo AF: 0.141

Asia WGS AF: 0.233 AC: 810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs2033214; hg19: chr16-24577520;