chr13-48303683-C-T

Variant names:

• chr13-48303683-C-T
• rs1376677344
• ENST00000433480.4:n.41G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000433480.4(RB1-DT):​n.41G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RB1-DT ENST00000433480.4 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04
• 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• retinoblastoma

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

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000433480.4. 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
	RB1-DT	NR_046414.2		n.20G>A		non_coding_transcript_exon	Exon 1 of 3
	RB1	NM_000321.3	MANE Select	c.-230C>T		upstream_gene	N/A	NP_000312.2	P06400
	RB1	NM_001407165.1		c.-230C>T		upstream_gene	N/A	NP_001394094.1	A0A3B3IS71

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RB1-DT	ENST00000433480.4	TSL:1	n.41G>A		non_coding_transcript_exon	Exon 1 of 3
	RB1-DT	ENST00000436963.3	TSL:3	n.38G>A		non_coding_transcript_exon	Exon 1 of 3
	RB1-DT	ENST00000700890.2		n.41G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 451934 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 235720

African (AFR) AF: 0.00 AC: 0 AN: 8860

American (AMR) AF: 0.00 AC: 0 AN: 9728

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12172

East Asian (EAS) AF: 0.00 AC: 0 AN: 23416

South Asian (SAS) AF: 0.00 AC: 0 AN: 40996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1912

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 302764

Other (OTH) AF: 0.00 AC: 0 AN: 24842

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000540 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Retinoblastoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.95
PhyloP100		1.0
PromoterAI		-0.095	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1376677344; hg19: chr13-48877819;