Variant 20-37082050-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.25

Variant links:

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]

RBL1 links:

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ACMG classification

Classification made for transcript

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	UniProt
RBL1	NM_002895.5 linkuse as main transcript	c.290+6939A>G		intron_variant		ENST00000373664.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
RBL1	ENST00000373664.8 linkuse as main transcript	c.290+6939A>G	intron_variant	1	NM_002895.5	P1	P28749-1
RBL1	ENST00000344359.7 linkuse as main transcript	c.290+6939A>G	intron_variant	1			P28749-2
RBL1	ENST00000527999.1 linkuse as main transcript	c.291-21A>G	intron_variant, NMD_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.579

AC:

88007

AN:

151908

Hom.:

26706

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.492

AC XY:

84891

AN XY:

172718

show subpopulations

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.:

AF XY:

0.577

AC XY:

42874

AN XY:

74316

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over