chr16-53441738-A-G

Variant names:

• chr16-53441738-A-G
• rs9921587
• NM_005611.4:c.372-920A>G

Variant summary

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

The NM_005611.4(RBL2):​c.372-920A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,054 control chromosomes in the GnomAD database, including 25,038 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 (25038 hom., cov: 31)
• Consequence: RBL2 NM_005611.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.619
• Publications: 19 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBL2	NM_005611.4	MANE Select	c.372-920A>G		intron	N/A	NP_005602.3
	RBL2	NM_001323608.2		c.372-920A>G		intron	N/A	NP_001310537.1
	RBL2	NM_001323609.2		c.372-920A>G		intron	N/A	NP_001310538.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBL2	ENST00000262133.11	TSL:1 MANE Select	c.372-920A>G		intron	N/A	ENSP00000262133.6
	RBL2	ENST00000544405.6	TSL:2	c.150-920A>G		intron	N/A	ENSP00000443744.2
	RBL2	ENST00000567964.6	TSL:5	c.-22-920A>G		intron	N/A	ENSP00000462464.1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82739 AN: 151936 Hom.: 24985 Cov.: 31

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.545 AC: 82847 AN: 152054 Hom.: 25038 Cov.: 31 AF XY: 0.534 AC XY: 39716 AN XY: 74328

African (AFR) AF: 0.808 AC: 33502 AN: 41476

American (AMR) AF: 0.447 AC: 6823 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2056 AN: 3470

East Asian (EAS) AF: 0.181 AC: 935 AN: 5168

South Asian (SAS) AF: 0.470 AC: 2263 AN: 4820

European-Finnish (FIN) AF: 0.348 AC: 3676 AN: 10558

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31846 AN: 67972

Other (OTH) AF: 0.553 AC: 1170 AN: 2114

Alfa AF: 0.490 Hom.: 9877

Bravo AF: 0.558

Asia WGS AF: 0.426 AC: 1488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.89
DANN	Benign	0.80
PhyloP100		-0.62
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: rs9921587; hg19: chr16-53475650; COSMIC: COSV50878746; COSMIC: COSV50878746;