rs17800727

chr16-53447098-A-Gchr16-53447098-A-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.10

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]

ACMG classification

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	UniProt
RBL2	NM_005611.4	c.629A>G	p.Tyr210Cys	missense_variant	4/22	ENST00000262133.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBL2	ENST00000262133.11	c.629A>G	p.Tyr210Cys	missense_variant	4/22	1	NM_005611.4	P1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31270 AN: 151752 Hom.: 4359 Cov.: 32

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

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.: 24 AF XY: 0.264 AC XY: 182106 AN XY: 689272

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.: 32 AF XY: 0.202 AC XY: 14980 AN XY: 74216

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	T
BayesDel_noAF	Benign	-0.16
Cadd	Pathogenic	27
Dann	Uncertain	1.0
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.77	T;T;T
MetaRNN	Benign	0.0018	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.13	P
PrimateAI	Uncertain	0.70	T
Sift4G	Benign	0.14	T;T;T
Polyphen		1.0	.;D;.
Vest4		0.63
MPC		0.88
ClinPred		1.0	D
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

Other links and lift over

dbSNP: rs17800727; hg19: chr16-53481010; COSMIC: COSV50883543; COSMIC: COSV50883543;