16-24567137-T-C

Variant names:

• chr16-24567137-T-C
• rs7195386
• NM_006910.5:c.1590-6T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006910.5(RBBP6):​c.1590-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,604,408 control chromosomes in the GnomAD database, including 237,587 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (30175 hom., cov: 31)
  • Exomes 𝑓: 0.53 (207412 hom.)
• Consequence: RBBP6 NM_006910.5 splice_region, intron
• Scores: Splicing: ADA: 0.00002483
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.786
• Publications: 29 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBBP6	NM_006910.5	MANE Select	c.1590-6T>C		splice_region intron	N/A	NP_008841.2
	RBBP6	NM_018703.4		c.1590-6T>C		splice_region intron	N/A	NP_061173.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBBP6	ENST00000319715.10	TSL:1 MANE Select	c.1590-6T>C		splice_region intron	N/A	ENSP00000317872.4
	RBBP6	ENST00000348022.6	TSL:1	c.1590-6T>C		splice_region intron	N/A	ENSP00000316291.4
	RBBP6	ENST00000381039.7	TSL:1	c.1290-3739T>C		intron	N/A	ENSP00000370427.3

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92911 AN: 151964 Hom.: 30126 Cov.: 31

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.605

GnomAD2 exomes AF: 0.559 AC: 137964 AN: 246708 AF XY: 0.560

Gnomad AFR exome AF: 0.843

Gnomad AMR exome AF: 0.581

Gnomad ASJ exome AF: 0.550

Gnomad EAS exome AF: 0.401

Gnomad FIN exome AF: 0.510

Gnomad NFE exome AF: 0.509

Gnomad OTH exome AF: 0.545

GnomAD4 exome AF: 0.529 AC: 768351 AN: 1452324 Hom.: 207412 Cov.: 45 AF XY: 0.533 AC XY: 383945 AN XY: 721012

African (AFR) AF: 0.849 AC: 28236 AN: 33260

American (AMR) AF: 0.583 AC: 25947 AN: 44472

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 14073 AN: 25908

East Asian (EAS) AF: 0.407 AC: 16083 AN: 39468

South Asian (SAS) AF: 0.695 AC: 59848 AN: 86062

European-Finnish (FIN) AF: 0.509 AC: 27070 AN: 53226

Middle Eastern (MID) AF: 0.580 AC: 3325 AN: 5732

European-Non Finnish (NFE) AF: 0.508 AC: 560759 AN: 1104230

Other (OTH) AF: 0.550 AC: 33010 AN: 59966

GnomAD4 genome AF: 0.612 AC: 93010 AN: 152084 Hom.: 30175 Cov.: 31 AF XY: 0.613 AC XY: 45535 AN XY: 74338

African (AFR) AF: 0.836 AC: 34707 AN: 41494

American (AMR) AF: 0.608 AC: 9284 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1922 AN: 3470

East Asian (EAS) AF: 0.413 AC: 2132 AN: 5164

South Asian (SAS) AF: 0.702 AC: 3383 AN: 4818

European-Finnish (FIN) AF: 0.512 AC: 5404 AN: 10562

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34338 AN: 67974

Other (OTH) AF: 0.606 AC: 1281 AN: 2114

Alfa AF: 0.544 Hom.: 74673

Bravo AF: 0.625

Asia WGS AF: 0.596 AC: 2072 AN: 3478

EpiCase AF: 0.506

EpiControl AF: 0.508

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.68
PhyloP100		0.79
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0040
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: rs7195386; hg19: chr16-24578458; COSMIC: COSV60503219;