rs10748

Positions:

• chr16-53470809-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000262133.11(RBL2):​c.2590T>C​(p.Leu864=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,613,868 control chromosomes in the GnomAD database, including 186,193 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 0.54 (24222 hom., cov: 32)
  • Exomes 𝑓: 0.46 (161971 hom.)
• Consequence: RBL2 ENST00000262133.11 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=1.64 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBL2	NM_005611.4	c.2590T>C	p.Leu864=	synonymous_variant	17/22	ENST00000262133.11	NP_005602.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBL2	ENST00000262133.11	c.2590T>C	p.Leu864=	synonymous_variant	17/22	1	NM_005611.4	ENSP00000262133	P1
RBL2	ENST00000379935.8	n.2289T>C		non_coding_transcript_exon_variant	16/21	1
RBL2	ENST00000680543.1	n.4381T>C		non_coding_transcript_exon_variant	15/21

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81716 AN: 151962 Hom.: 24178 Cov.: 32

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.545

GnomAD3 exomes AF: 0.440 AC: 110554 AN: 251234 Hom.: 27043 AF XY: 0.445 AC XY: 60480 AN XY: 135818

Gnomad AFR exome AF: 0.782

Gnomad AMR exome AF: 0.286

Gnomad ASJ exome AF: 0.590

Gnomad EAS exome AF: 0.195

Gnomad SAS exome AF: 0.488

Gnomad FIN exome AF: 0.347

Gnomad NFE exome AF: 0.468

Gnomad OTH exome AF: 0.474

GnomAD4 exome AF: 0.462 AC: 675213 AN: 1461788 Hom.: 161971 Cov.: 55 AF XY: 0.464 AC XY: 337264 AN XY: 727204

Gnomad4 AFR exome AF: 0.794

Gnomad4 AMR exome AF: 0.303

Gnomad4 ASJ exome AF: 0.588

Gnomad4 EAS exome AF: 0.170

Gnomad4 SAS exome AF: 0.487

Gnomad4 FIN exome AF: 0.353

Gnomad4 NFE exome AF: 0.467

Gnomad4 OTH exome AF: 0.491

GnomAD4 genome AF: 0.538 AC: 81813 AN: 152080 Hom.: 24222 Cov.: 32 AF XY: 0.528 AC XY: 39268 AN XY: 74350

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.550

Alfa AF: 0.499 Hom.: 25305

Bravo AF: 0.550

Asia WGS AF: 0.426 AC: 1486 AN: 3478

EpiCase AF: 0.490

EpiControl AF: 0.506

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.3
DANN	Benign	0.46

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: rs10748; hg19: chr16-53504721; COSMIC: COSV50877123; COSMIC: COSV50877123;