chr20-37003804-GCG-ACA

Variant names:

• chr20-37003804-GCG-ACA
• NM_002895.5:c.2932_2934delCGCinsTGT
• RBL1 p.Arg978Cys

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_002895.5(RBL1):​c.2932_2934delCGCinsTGT​(p.Arg978Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RBL1 NM_002895.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.45
• Publications: 0 publications found

Genes affected

RBL1 (HGNC:9893): (RB transcriptional corepressor like 1) The protein encoded by this gene is similar in sequence and possibly function to the product of the retinoblastoma 1 (RB1) gene. The RB1 gene product is a tumor suppressor protein that appears to be involved in cell cycle regulation, as it is phosphorylated in the S to M phase transition and is dephosphorylated in the G1 phase of the cell cycle. Both the RB1 protein and the product of this gene can form a complex with adenovirus E1A protein and SV40 large T-antigen, with the SV40 large T-antigen binding only to the unphosphorylated form of each protein. In addition, both proteins can inhibit the transcription of cell cycle genes containing E2F binding sites in their promoters. Due to the sequence and biochemical similarities with the RB1 protein, it is thought that the protein encoded by this gene may also be a tumor suppressor. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002895.5. 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
	RBL1	NM_002895.5	MANE Select	c.2932_2934delCGCinsTGT	p.Arg978Cys	missense	N/A	NP_002886.2
	RBL1	NM_183404.4		c.2932_2934delCGCinsTGT	p.Arg978Cys	missense	N/A	NP_899662.1	P28749-2
	RBL1	NM_001323281.2		c.1651_1653delCGCinsTGT	p.Arg551Cys	missense	N/A	NP_001310210.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBL1	ENST00000373664.8	TSL:1 MANE Select	c.2932_2934delCGCinsTGT	p.Arg978Cys	missense	N/A	ENSP00000362768.3	P28749-1
	RBL1	ENST00000344359.7	TSL:1	c.2932_2934delCGCinsTGT	p.Arg978Cys	missense	N/A	ENSP00000343646.3	P28749-2
	RBL1	ENST00000927852.1		c.2326_2328delCGCinsTGT	p.Arg776Cys	missense	N/A	ENSP00000597911.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-35632207;