rs387906520

Variant names:

• chr13-48303724-G-A
• rs387906520
• NM_000321.3:c.-189G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-48303724-G-A
• chr13-48303724-G-T

Variant summary

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

The NM_000321.3(RB1):​c.-189G>A variant causes a upstream gene change. The variant allele was found at a frequency of 0.00000128 in 780,022 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000013 (0 hom.)
• Consequence: RB1 NM_000321.3 upstream_gene
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.76
• Publications: 0 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-DT (HGNC:42778): (RB1 divergent transcript)

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=-0.23).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000321.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RB1	NM_000321.3	MANE Select	c.-189G>A		upstream_gene	N/A	NP_000312.2
	RB1	NM_001407165.1		c.-189G>A		upstream_gene	N/A	NP_001394094.1
	RB1	NM_001407166.1		c.-189G>A		upstream_gene	N/A	NP_001394095.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RB1	ENST00000267163.6	TSL:1 MANE Select	c.-189G>A		upstream_gene	N/A	ENSP00000267163.4
	RB1-DT	ENST00000433480.4	TSL:1	n.-1C>T		upstream_gene	N/A
	RB1	ENST00000467505.6	TSL:1	n.-189G>A		upstream_gene	N/A	ENSP00000434702.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000128 AC: 1 AN: 780022 Hom.: 0 Cov.: 11 AF XY: 0.00000256 AC XY: 1 AN XY: 390144

African (AFR) AF: 0.00 AC: 0 AN: 15096

American (AMR) AF: 0.00 AC: 0 AN: 12014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14948

East Asian (EAS) AF: 0.00 AC: 0 AN: 25312

South Asian (SAS) AF: 0.00 AC: 0 AN: 49094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2584

European-Non Finnish (NFE) AF: 0.00000168 AC: 1 AN: 596264

Other (OTH) AF: 0.00 AC: 0 AN: 35820

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

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	-0.23
CADD	Benign	22
DANN	Uncertain	0.98
PhyloP100		3.8
PromoterAI		-0.79	Under-expression

Splicing

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

Other links and lift over

dbSNP: rs387906520; hg19: chr13-48877860;