chr16-53446296-G-A

Variant names:

• chr16-53446296-G-A
• rs10521289
• NM_005611.4:c.573-746G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005611.4(RBL2):​c.573-746G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0524 in 151,578 control chromosomes in the GnomAD database, including 627 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 0.052 (627 hom., cov: 33)
• Consequence: RBL2 NM_005611.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214
• Publications: 1 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005611.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBL2	NM_005611.4	MANE Select	c.573-746G>A		intron	N/A	NP_005602.3
	RBL2	NM_001323608.2		c.573-746G>A		intron	N/A	NP_001310537.1	Q08999-1
	RBL2	NM_001323609.2		c.573-746G>A		intron	N/A	NP_001310538.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBL2	ENST00000262133.11	TSL:1 MANE Select	c.573-746G>A		intron	N/A	ENSP00000262133.6	Q08999-1
	RBL2	ENST00000379935.8	TSL:1	n.149+367G>A		intron	N/A
	RBL2	ENST00000894791.1		c.573-746G>A		intron	N/A	ENSP00000564850.1

Frequencies

GnomAD3 genomes AF: 0.0521 AC: 7894 AN: 151458 Hom.: 618 Cov.: 33

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0255

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.00202

Gnomad OTH AF: 0.0383

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0524 AC: 7937 AN: 151578 Hom.: 627 Cov.: 33 AF XY: 0.0506 AC XY: 3753 AN XY: 74108

African (AFR) AF: 0.177 AC: 7272 AN: 41062

American (AMR) AF: 0.0255 AC: 388 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3460

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.000417 AC: 2 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.0479 AC: 14 AN: 292

European-Non Finnish (NFE) AF: 0.00202 AC: 137 AN: 67962

Other (OTH) AF: 0.0379 AC: 80 AN: 2110

Alfa AF: 0.0197 Hom.: 103

Bravo AF: 0.0589

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.9
DANN	Benign	0.27
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10521289; hg19: chr16-53480208;