chr16-53479121-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005611.4(RBL2):​c.2704-33C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,399,716 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: RBL2 NM_005611.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510
• 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

ENSG00000279344 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000429 AC: 6 AN: 1399716 Hom.: 0 Cov.: 25 AF XY: 0.00000143 AC XY: 1 AN XY: 700140

African (AFR) AF: 0.00 AC: 0 AN: 31958

American (AMR) AF: 0.00 AC: 0 AN: 44542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25744

East Asian (EAS) AF: 0.00 AC: 0 AN: 39490

South Asian (SAS) AF: 0.00 AC: 0 AN: 84948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5638

European-Non Finnish (NFE) AF: 0.00000568 AC: 6 AN: 1055736

Other (OTH) AF: 0.00 AC: 0 AN: 58300

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.29
PhyloP100		-0.051

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: rs8043918; hg19: chr16-53513033;