16-24555887-A-C

Variant names:

• chr16-24555887-A-C
• rs61759886
• NM_006910.5:c.504A>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_006910.5(RBBP6):​c.504A>C​(p.Gly168Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0064 in 1,607,360 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0066 (27 hom.)
• Consequence: RBBP6 NM_006910.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.02
• Publications: 5 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 16-24555887-A-C is Benign according to our data. Variant chr16-24555887-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2443232.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.02 with no splicing effect.
• BS2: High AC in GnomAd4 at 711 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.504A>C	p.Gly168Gly	synonymous	Exon 6 of 18	NP_008841.2
	RBBP6	NM_018703.4		c.504A>C	p.Gly168Gly	synonymous	Exon 6 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.504A>C	p.Gly168Gly	synonymous	Exon 6 of 18	ENSP00000317872.4	Q7Z6E9-1
	RBBP6	ENST00000348022.6	TSL:1	c.504A>C	p.Gly168Gly	synonymous	Exon 6 of 17	ENSP00000316291.4	Q7Z6E9-2
	RBBP6	ENST00000381039.7	TSL:1	c.504A>C	p.Gly168Gly	synonymous	Exon 6 of 11	ENSP00000370427.3	Q7Z6E9-4

Frequencies

GnomAD3 genomes AF: 0.00467 AC: 711 AN: 152194 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00778

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00433 AC: 1087 AN: 251290 AF XY: 0.00445

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00379

Gnomad NFE exome AF: 0.00796

Gnomad OTH exome AF: 0.00327

GnomAD4 exome AF: 0.00658 AC: 9581 AN: 1455048 Hom.: 27 Cov.: 31 AF XY: 0.00624 AC XY: 4522 AN XY: 724366

African (AFR) AF: 0.00102 AC: 34 AN: 33312

American (AMR) AF: 0.00197 AC: 88 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0000767 AC: 2 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86120

European-Finnish (FIN) AF: 0.00416 AC: 222 AN: 53402

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5758

European-Non Finnish (NFE) AF: 0.00807 AC: 8921 AN: 1105820

Other (OTH) AF: 0.00515 AC: 310 AN: 60182

GnomAD4 genome AF: 0.00467 AC: 711 AN: 152312 Hom.: 2 Cov.: 32 AF XY: 0.00424 AC XY: 316 AN XY: 74464

African (AFR) AF: 0.00164 AC: 68 AN: 41572

American (AMR) AF: 0.00314 AC: 48 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00339 AC: 36 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00778 AC: 529 AN: 68030

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00598 Hom.: 3

Bravo AF: 0.00468

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00692

EpiControl AF: 0.00729

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		-1.0
PromoterAI		0.048	Neutral
Mutation Taster		=92/8	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: rs61759886; hg19: chr16-24567208; COSMIC: COSV100154890; COSMIC: COSV100154890;