Variant rs17800727 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005611.4(RBL2):c.629A>G(p.Tyr210Cys) variant causes a missense change. The variant allele was found at a frequency of 0.26 in 1,530,708 control chromosomes in the GnomAD database, including 58,385 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.21 ( 4358 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54027 hom. )

Consequence

RBL2
NM_005611.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.10

Variant links:

Genes affected

RBL2 (HGNC:9894): (RB transcriptional corepressor like 2) Enables promoter-specific chromatin binding activity. Involved in regulation of lipid kinase activity. Acts upstream of or within negative regulation of gene expression. Located in chromosome; cytosol; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

RBL2 links:

RBL2 (HGNC:):

RBL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017870069).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBL2	NM_005611.4 linkuse as main transcript	c.629A>G	p.Tyr210Cys	missense_variant	4/22	ENST00000262133.11	NP_005602.3	Q08999-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBL2	ENST00000262133.11 linkuse as main transcript	c.629A>G	p.Tyr210Cys	missense_variant	4/22	1	NM_005611.4	ENSP00000262133.6		Q08999-1

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31270

AN:

151752

Hom.:

4359

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0524

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.284

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0982

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.306

Gnomad OTH

AF:

0.245

GnomAD3 exomes

AF:

0.212

AC:

50257

AN:

236672

Hom.:

6826

AF XY:

0.218

AC XY:

28089

AN XY:

128566

show subpopulations

Gnomad AFR exome

AF:

0.0432

Gnomad AMR exome

AF:

0.146

Gnomad ASJ exome

AF:

0.288

Gnomad EAS exome

AF:

0.000411

Gnomad SAS exome

AF:

0.104

Gnomad FIN exome

AF:

0.238

Gnomad NFE exome

AF:

0.302

Gnomad OTH exome

AF:

0.250

GnomAD4 exome

AF:

0.266

AC:

366938

AN:

1378840

Hom.:

54027

Cov.:

AF XY:

0.264

AC XY:

182106

AN XY:

689272

show subpopulations

Gnomad4 AFR exome

AF:

0.0418

Gnomad4 AMR exome

AF:

0.157

Gnomad4 ASJ exome

AF:

0.288

Gnomad4 EAS exome

AF:

0.000310

Gnomad4 SAS exome

AF:

0.109

Gnomad4 FIN exome

AF:

0.249

Gnomad4 NFE exome

AF:

0.301

Gnomad4 OTH exome

AF:

0.248

GnomAD4 genome

AF:

0.206

AC:

31261

AN:

151868

Hom.:

4358

Cov.:

AF XY:

0.202

AC XY:

14980

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.0522

Gnomad4 AMR

AF:

0.231

Gnomad4 ASJ

AF:

0.284

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.0981

Gnomad4 FIN

AF:

0.237

Gnomad4 NFE

AF:

0.306

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.262

Hom.:

5336

Bravo

AF:

0.198

TwinsUK

AF:

0.298

AC:

1106

ALSPAC

AF:

0.289

AC:

1113

ESP6500AA

AF:

0.0530

AC:

233

ESP6500EA

AF:

0.308

AC:

2647

ExAC

AF:

0.214

AC:

26007

Asia WGS

AF:

0.0550

AC:

191

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

.;T;.

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.77

T;T;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.30

.;N;.

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.2

.;D;D

REVEL

Uncertain

0.30

Sift

Benign

0.26

.;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

1.0

.;D;.

Vest4

0.63

MPC

0.88

ClinPred

1.0

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.22

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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