13-48485441-C-T

Variant names:

• chr13-48485441-C-T
• rs990814
• ENST00000643064.1:c.192+103998C>T

Variant summary

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

The ENST00000643064.1(RB1):​c.192+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
• 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=-0.9).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RB1	ENST00000643064.1	c.192+103998C>T		intron_variant	Intron 1 of 1			ENSP00000496005.1

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

African (AFR) AF: 0.192 AC: 7958 AN: 41454

American (AMR) AF: 0.685 AC: 10467 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2491 AN: 3472

East Asian (EAS) AF: 0.640 AC: 3309 AN: 5174

South Asian (SAS) AF: 0.651 AC: 3128 AN: 4806

European-Finnish (FIN) AF: 0.704 AC: 7440 AN: 10562

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48693 AN: 67958

Other (OTH) AF: 0.605 AC: 1280 AN: 2114

Alfa AF: 0.643 Hom.: 21289

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
PhyloP100		-0.52

Splicing

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

Other links and lift over

dbSNP: rs990814; hg19: chr13-49059577;