rs1899069024

Variant names:

• chr16-24561938-C-A
• rs1899069024
• NM_006910.5:c.1066C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-24561938-C-A
• chr16-24561938-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006910.5(RBBP6):​c.1066C>A​(p.Pro356Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: RBBP6 NM_006910.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.12
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24346301).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006910.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBBP6	NM_006910.5	MANE Select	c.1066C>A	p.Pro356Thr	missense	Exon 10 of 18	NP_008841.2
	RBBP6	NM_018703.4		c.1066C>A	p.Pro356Thr	missense	Exon 10 of 17	NP_061173.1	Q7Z6E9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBBP6	ENST00000319715.10	TSL:1 MANE Select	c.1066C>A	p.Pro356Thr	missense	Exon 10 of 18	ENSP00000317872.4	Q7Z6E9-1
	RBBP6	ENST00000348022.6	TSL:1	c.1066C>A	p.Pro356Thr	missense	Exon 10 of 17	ENSP00000316291.4	Q7Z6E9-2
	RBBP6	ENST00000381039.7	TSL:1	c.1066C>A	p.Pro356Thr	missense	Exon 10 of 11	ENSP00000370427.3	Q7Z6E9-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461572 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727128

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111726

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	0.0025	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.97	L
PhyloP100		4.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.21
Sift	Benign	0.048	D
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.44
MutPred		0.20		Loss of loop (P = 0.0153)
MVP		0.45
MPC		0.22
ClinPred		0.91	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.69
Mutation Taster		=66/34	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: rs1899069024; hg19: chr16-24573259;