chr16-24567137-T-C

Position:

• chr16-24567137-T-C

Variant summary

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

The NM_006910.5(RBBP6):​c.1590-6T>C variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002483
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.786

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=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBBP6	NM_006910.5	c.1590-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000319715.10	NP_008841.2
RBBP6	NM_018703.4	c.1590-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_061173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBBP6	ENST00000319715.10	c.1590-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006910.5	ENSP00000317872	P3

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

GnomAD3 exomes AF: 0.559 AC: 137964 AN: 246708 Hom.: 40117 AF XY: 0.560 AC XY: 74831 AN XY: 133624

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 SAS exome AF: 0.701

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

Gnomad4 AFR exome AF: 0.849

Gnomad4 AMR exome AF: 0.583

Gnomad4 ASJ exome AF: 0.543

Gnomad4 EAS exome AF: 0.407

Gnomad4 SAS exome AF: 0.695

Gnomad4 FIN exome AF: 0.509

Gnomad4 NFE exome AF: 0.508

Gnomad4 OTH exome AF: 0.550

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

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.606

Alfa AF: 0.528 Hom.: 30799

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs7195386; hg19: chr16-24578458; COSMIC: COSV60503219;