13-48303701-G-T

Variant names:

• chr13-48303701-G-T
• rs1952048420
• ENST00000433480.4:n.23C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000433480.4(RB1-DT):​n.23C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000174 in 574,070 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: RB1-DT ENST00000433480.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17
• Publications: 0 publications found

Genes affected

RB1-DT (HGNC:42778): (RB1 divergent transcript)

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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RB1	NM_000321.3	c.-212G>T		upstream_gene_variant		ENST00000267163.6	NP_000312.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RB1	ENST00000267163.6	c.-212G>T		upstream_gene_variant		1	NM_000321.3	ENSP00000267163.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000174 AC: 1 AN: 574070 Hom.: 0 Cov.: 8 AF XY: 0.00000341 AC XY: 1 AN XY: 293620

African (AFR) AF: 0.00 AC: 0 AN: 11152

American (AMR) AF: 0.00 AC: 0 AN: 10388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13100

East Asian (EAS) AF: 0.00 AC: 0 AN: 24296

South Asian (SAS) AF: 0.00 AC: 0 AN: 43584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2118

European-Non Finnish (NFE) AF: 0.00000243 AC: 1 AN: 412286

Other (OTH) AF: 0.00 AC: 0 AN: 29052

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Benign	0.97
PhyloP100		2.2
PromoterAI		-0.63	Under-expression

Splicing

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

Other links and lift over

dbSNP: rs1952048420; hg19: chr13-48877837;