20-37082050-T-C

Position:

• chr20-37082050-T-C

Variant summary

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

The ENST00000373664.8(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 ENST00000373664.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBL1	NM_002895.5	c.290+6939A>G		intron_variant		ENST00000373664.8	NP_002886.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBL1	ENST00000373664.8	c.290+6939A>G		intron_variant		1	NM_002895.5	ENSP00000362768	P1
RBL1	ENST00000344359.7	c.290+6939A>G		intron_variant		1		ENSP00000343646
RBL1	ENST00000527999.1	c.291-21A>G		intron_variant, NMD_transcript_variant		5		ENSP00000437240

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

GnomAD3 exomes AF: 0.507 AC: 64644 AN: 127382 Hom.: 16790 AF XY: 0.500 AC XY: 34908 AN XY: 69766

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 SAS exome AF: 0.429

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

Gnomad4 AFR exome AF: 0.772

Gnomad4 AMR exome AF: 0.495

Gnomad4 ASJ exome AF: 0.473

Gnomad4 EAS exome AF: 0.520

Gnomad4 SAS exome AF: 0.427

Gnomad4 FIN exome AF: 0.573

Gnomad4 NFE exome AF: 0.507

Gnomad4 OTH exome AF: 0.518

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

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.573

Alfa AF: 0.514 Hom.: 10736

Bravo AF: 0.586

Asia WGS AF: 0.480 AC: 1673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.80
DANN	Benign	0.29

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: rs1892205; hg19: chr20-35710453;