NM_002895.5:c.290+6939A>T

Variant names:

• chr20-37082050-T-A
• rs1892205
• NM_002895.5:c.290+6939A>T

Variant summary

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

The NM_002895.5(RBL1):​c.290+6939A>T variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RBL1 NM_002895.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25
• Publications: 4 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: 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=-0.96).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBL1	NM_002895.5	MANE Select	c.290+6939A>T		intron	N/A	NP_002886.2
	RBL1	NM_183404.4		c.290+6939A>T		intron	N/A	NP_899662.1
	RBL1	NM_001323281.2		c.-1065+6939A>T		intron	N/A	NP_001310210.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBL1	ENST00000373664.8	TSL:1 MANE Select	c.290+6939A>T		intron	N/A	ENSP00000362768.3
	RBL1	ENST00000344359.7	TSL:1	c.290+6939A>T		intron	N/A	ENSP00000343646.3
	RBL1	ENST00000527999.1	TSL:5	n.291-21A>T		intron	N/A	ENSP00000437240.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 303420 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 172818

African (AFR) AF: 0.00 AC: 0 AN: 8608

American (AMR) AF: 0.00 AC: 0 AN: 27184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10760

East Asian (EAS) AF: 0.00 AC: 0 AN: 9196

South Asian (SAS) AF: 0.00 AC: 0 AN: 59652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 158734

Other (OTH) AF: 0.00 AC: 0 AN: 14212

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.62
DANN	Benign	0.43
PhyloP100		-2.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1892205; hg19: chr20-35710453;