16-53479121-C-T

Variant names:

• chr16-53479121-C-T
• rs8043918
• NM_005611.4:c.2704-33C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 publications found

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 Gene-Disease associations (from GenCC):

• Brunet-Wagner neurodevelopmental syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000279344 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RBL2	NM_005611.4	c.2704-33C>T		intron_variant	Intron 17 of 21	ENST00000262133.11	NP_005602.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBL2	ENST00000262133.11	c.2704-33C>T		intron_variant	Intron 17 of 21	1	NM_005611.4	ENSP00000262133.6
RBL2	ENST00000379935.8	n.2403-33C>T		intron_variant	Intron 16 of 20	1
ENSG00000279344	ENST00000624289.1	n.2430G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
RBL2	ENST00000680543.1	n.4495-33C>T		intron_variant	Intron 15 of 20

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

GnomAD2 exomes AF: 0.427 AC: 106757 AN: 250174 AF XY: 0.435

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 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

African (AFR) AF: 0.636 AC: 20269 AN: 31872

American (AMR) AF: 0.291 AC: 12957 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 14799 AN: 25710

East Asian (EAS) AF: 0.169 AC: 6690 AN: 39470

South Asian (SAS) AF: 0.484 AC: 41064 AN: 84840

European-Finnish (FIN) AF: 0.353 AC: 18825 AN: 53328

Middle Eastern (MID) AF: 0.554 AC: 3115 AN: 5626

European-Non Finnish (NFE) AF: 0.460 AC: 483219 AN: 1050764

Other (OTH) AF: 0.473 AC: 27513 AN: 58114

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

African (AFR) AF: 0.629 AC: 26084 AN: 41448

American (AMR) AF: 0.425 AC: 6489 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2014 AN: 3470

East Asian (EAS) AF: 0.181 AC: 937 AN: 5184

South Asian (SAS) AF: 0.469 AC: 2258 AN: 4812

European-Finnish (FIN) AF: 0.349 AC: 3689 AN: 10574

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31754 AN: 67978

Other (OTH) AF: 0.516 AC: 1088 AN: 2110

Alfa AF: 0.486 Hom.: 32112

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
PhyloP100		-0.051
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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

Other links and lift over

dbSNP: rs8043918; hg19: chr16-53513033; COSMIC: COSV107256428; COSMIC: COSV107256428;