rs4151636

Positions:

• chr13-48482598-C-G

Variant summary

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

The ENST00000643064.1(RB1):​c.194+101155C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 152,248 control chromosomes in the GnomAD database, including 168 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 0.038 (168 hom., cov: 32)
• Consequence: RB1 ENST00000643064.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.866

Genes affected

RB1 (HGNC:9884): (RB transcriptional corepressor 1) The protein encoded by this gene is a negative regulator of the cell cycle and was the first tumor suppressor gene found. The encoded protein also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. The active, hypophosphorylated form of the protein binds transcription factor E2F1. Defects in this gene are a cause of childhood cancer retinoblastoma (RB), bladder cancer, and osteogenic sarcoma. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RB1	ENST00000643064.1	c.194+101155C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0379 AC: 5767 AN: 152130 Hom.: 168 Cov.: 32

Gnomad AFR AF: 0.00857

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0580

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0729

Gnomad FIN AF: 0.0768

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0456

Gnomad OTH AF: 0.0373

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

GnomAD4 genome AF: 0.0379 AC: 5766 AN: 152248 Hom.: 168 Cov.: 32 AF XY: 0.0401 AC XY: 2986 AN XY: 74426

Gnomad4 AFR AF: 0.00854

Gnomad4 AMR AF: 0.0579

Gnomad4 ASJ AF: 0.0207

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0730

Gnomad4 FIN AF: 0.0768

Gnomad4 NFE AF: 0.0457

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0395 Hom.: 16

Bravo AF: 0.0350

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.4
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4151636; hg19: chr13-49056734;