rs4151636

Variant names:

• chr13-48482598-C-G
• rs4151636
• ENST00000643064.1:c.192+101155C>G

Variant summary

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

The ENST00000643064.1(RB1):​c.192+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
• Publications: 7 publications found

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]

RB1 Gene-Disease associations (from GenCC):

• hereditary retinoblastoma

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics
• retinoblastoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• melanoma

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000643064.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RB1	ENST00000643064.1		c.192+101155C>G		intron	N/A	ENSP00000496005.1

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

African (AFR) AF: 0.00854 AC: 355 AN: 41546

American (AMR) AF: 0.0579 AC: 885 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 72 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5182

South Asian (SAS) AF: 0.0730 AC: 352 AN: 4822

European-Finnish (FIN) AF: 0.0768 AC: 814 AN: 10600

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0457 AC: 3106 AN: 68020

Other (OTH) AF: 0.0369 AC: 78 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.4
DANN	Benign	0.73
PhyloP100		0.87

Splicing

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

Other links and lift over

dbSNP: rs4151636; hg19: chr13-49056734;