chr20-37044653-C-T

Position:

• chr20-37044653-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002895.5(RBL1):​c.1606-403G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,110 control chromosomes in the GnomAD database, including 7,896 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 0.29 (7896 hom., cov: 32)
• Consequence: RBL1 NM_002895.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBL1	NM_002895.5	c.1606-403G>A		intron_variant		ENST00000373664.8	NP_002886.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBL1	ENST00000373664.8	c.1606-403G>A		intron_variant		1	NM_002895.5	ENSP00000362768.3
RBL1	ENST00000344359.7	c.1606-403G>A		intron_variant		1		ENSP00000343646.3

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44472 AN: 151992 Hom.: 7883 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.0339

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.293 AC: 44516 AN: 152110 Hom.: 7896 Cov.: 32 AF XY: 0.288 AC XY: 21434 AN XY: 74338

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.0340

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.295

Alfa AF: 0.239 Hom.: 2304

Bravo AF: 0.299

Asia WGS AF: 0.124 AC: 434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs3897903; hg19: chr20-35673056;