13-48485441-C-T

Variant summary

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

The ENST00000643064.1(RB1):c.194+103998C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,026 control chromosomes in the GnomAD database, including 28,172 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 0.56 (28172 hom., cov: 31)
• Consequence: RB1 ENST00000643064.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.711 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+103998C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85571 AN: 151908 Hom.: 28178 Cov.: 31

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.563 AC: 85569 AN: 152026 Hom.: 28172 Cov.: 31 AF XY: 0.566 AC XY: 42043 AN XY: 74310

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.717

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.605

Alfa AF: 0.639 Hom.: 14032

Bravo AF: 0.544

Asia WGS AF: 0.585 AC: 2037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.70
Dann	Benign	0.27

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs990814; hg19: chr13-49059577;