chr16-53437166-C-T

Variant names:

• chr16-53437166-C-T
• rs10521287
• NM_005611.4:c.241-1850C>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.241-1850C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0522 in 151,738 control chromosomes in the GnomAD database, including 619 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 (619 hom., cov: 32)
• Consequence: RBL2 NM_005611.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 0 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBL2	NM_005611.4	c.241-1850C>T		intron_variant	Intron 1 of 21	ENST00000262133.11	NP_005602.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBL2	ENST00000262133.11	c.241-1850C>T		intron_variant	Intron 1 of 21	1	NM_005611.4	ENSP00000262133.6
RBL2	ENST00000544405.6	c.18+1422C>T		intron_variant	Intron 1 of 14	2		ENSP00000443744.2
RBL2	ENST00000567964.6	c.-153-1850C>T		intron_variant	Intron 1 of 5	5		ENSP00000462464.1
RBL2	ENST00000680543.1	n.380-1850C>T		intron_variant	Intron 1 of 20

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7874 AN: 151622 Hom.: 609 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0253

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.0000958

Gnomad MID AF: 0.0443

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: 0.0522 AC: 7918 AN: 151738 Hom.: 619 Cov.: 32 AF XY: 0.0505 AC XY: 3746 AN XY: 74134

African (AFR) AF: 0.175 AC: 7252 AN: 41366

American (AMR) AF: 0.0252 AC: 384 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3468

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5170

South Asian (SAS) AF: 0.000624 AC: 3 AN: 4806

European-Finnish (FIN) AF: 0.0000958 AC: 1 AN: 10436

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.00202 AC: 137 AN: 67950

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

Alfa AF: 0.0357 Hom.: 56

Bravo AF: 0.0589

Asia WGS AF: 0.0150 AC: 52 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.1
DANN	Benign	0.72
PhyloP100		-0.093
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: rs10521287; hg19: chr16-53471078;