rs8043918

chr16-53479121-C-T

Variant summary

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

The NM_005611.4(RBL2):c.2704-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,546,302 control chromosomes in the GnomAD database, including 165,704 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 0.49 (19424 hom., cov: 32)
  • Exomes 𝑓: 0.45 (146280 hom.)
• Consequence: RBL2 NM_005611.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBL2	NM_005611.4	c.2704-33C>T		intron_variant		ENST00000262133.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBL2	ENST00000262133.11	c.2704-33C>T		intron_variant		1	NM_005611.4	P1
	ENST00000624289.1	n.2430G>A		non_coding_transcript_exon_variant	1/1
RBL2	ENST00000379935.8	n.2403-33C>T		intron_variant, non_coding_transcript_variant		1
RBL2	ENST00000680543.1	n.4495-33C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74820 AN: 151944 Hom.: 19406 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.511

GnomAD3 exomes AF: 0.427 AC: 106757 AN: 250174 Hom.: 24826 AF XY: 0.435 AC XY: 58839 AN XY: 135222

Gnomad AFR exome AF: 0.627

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.579

Gnomad EAS exome AF: 0.194

Gnomad SAS exome AF: 0.486

Gnomad FIN exome AF: 0.346

Gnomad NFE exome AF: 0.466

Gnomad OTH exome AF: 0.463

GnomAD4 exome AF: 0.451 AC: 628451 AN: 1394242 Hom.: 146280 Cov.: 25 AF XY: 0.454 AC XY: 316668 AN XY: 697602

Gnomad4 AFR exome AF: 0.636

Gnomad4 AMR exome AF: 0.291

Gnomad4 ASJ exome AF: 0.576

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.484

Gnomad4 FIN exome AF: 0.353

Gnomad4 NFE exome AF: 0.460

Gnomad4 OTH exome AF: 0.473

GnomAD4 genome AF: 0.492 AC: 74877 AN: 152060 Hom.: 19424 Cov.: 32 AF XY: 0.484 AC XY: 35953 AN XY: 74314

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.516

Alfa AF: 0.485 Hom.: 25616

Bravo AF: 0.499

Asia WGS AF: 0.410 AC: 1431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.0
Dann	Benign	0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs8043918; hg19: chr16-53513033;