20-37082050-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002895.5(RBL1):​c.290+6939A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 455,266 control chromosomes in the GnomAD database, including 65,725 homozygotes. 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: 𝑓 0.58 (26748 hom., cov: 32)
  • Exomes 𝑓: 0.50 (38977 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

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>G		intron	N/A	NP_002886.2
	RBL1	NM_183404.4		c.290+6939A>G		intron	N/A	NP_899662.1
	RBL1	NM_001323281.2		c.-1065+6939A>G		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>G		intron	N/A	ENSP00000362768.3
	RBL1	ENST00000344359.7	TSL:1	c.290+6939A>G		intron	N/A	ENSP00000343646.3
	RBL1	ENST00000527999.1	TSL:5	n.291-21A>G		intron	N/A	ENSP00000437240.1

Frequencies

GnomAD3 genomes AF: 0.579 AC: 88007 AN: 151908 Hom.: 26706 Cov.: 32

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.577

GnomAD2 exomes AF: 0.507 AC: 64644 AN: 127382 AF XY: 0.500

Gnomad AFR exome AF: 0.777

Gnomad AMR exome AF: 0.499

Gnomad ASJ exome AF: 0.474

Gnomad EAS exome AF: 0.524

Gnomad FIN exome AF: 0.577

Gnomad NFE exome AF: 0.509

Gnomad OTH exome AF: 0.504

GnomAD4 exome AF: 0.501 AC: 151853 AN: 303240 Hom.: 38977 Cov.: 0 AF XY: 0.492 AC XY: 84891 AN XY: 172718

African (AFR) AF: 0.772 AC: 6639 AN: 8600

American (AMR) AF: 0.495 AC: 13449 AN: 27148

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 5090 AN: 10750

East Asian (EAS) AF: 0.520 AC: 4779 AN: 9190

South Asian (SAS) AF: 0.427 AC: 25445 AN: 59620

European-Finnish (FIN) AF: 0.573 AC: 7079 AN: 12352

Middle Eastern (MID) AF: 0.561 AC: 1525 AN: 2716

European-Non Finnish (NFE) AF: 0.507 AC: 80487 AN: 158656

Other (OTH) AF: 0.518 AC: 7360 AN: 14208

GnomAD4 genome AF: 0.580 AC: 88101 AN: 152026 Hom.: 26748 Cov.: 32 AF XY: 0.577 AC XY: 42874 AN XY: 74316

African (AFR) AF: 0.774 AC: 32097 AN: 41472

American (AMR) AF: 0.489 AC: 7462 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1657 AN: 3466

East Asian (EAS) AF: 0.518 AC: 2681 AN: 5174

South Asian (SAS) AF: 0.417 AC: 2011 AN: 4820

European-Finnish (FIN) AF: 0.579 AC: 6126 AN: 10582

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34291 AN: 67938

Other (OTH) AF: 0.573 AC: 1207 AN: 2106

Alfa AF: 0.516 Hom.: 11976

Bravo AF: 0.586

Asia WGS AF: 0.480 AC: 1673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.80
DANN	Benign	0.29
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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;