rs2362772

Variant names:

• chr3-24876741-C-A
• rs2362772
• NM_001290216.3:c.-332+17989C>A

Variant summary

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

The NM_001290216.3(RARB):​c.-332+17989C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,082 control chromosomes in the GnomAD database, including 1,388 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 0.11 (1388 hom., cov: 32)
• Consequence: RARB NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348
• Publications: 3 publications found

Genes affected

RARB (HGNC:9865): (retinoic acid receptor beta) This gene encodes retinoic acid receptor beta, a member of the thyroid-steroid hormone receptor superfamily of nuclear transcriptional regulators. This receptor localizes to the cytoplasm and to subnuclear compartments. It binds retinoic acid, the biologically active form of vitamin A which mediates cellular signalling in embryonic morphogenesis, cell growth and differentiation. It is thought that this protein limits growth of many cell types by regulating gene expression. The gene was first identified in a hepatocellular carcinoma where it flanks a hepatitis B virus integration site. Alternate promoter usage and differential splicing result in multiple transcript variants. [provided by RefSeq, Mar 2014]

RARB Gene-Disease associations (from GenCC):

• microphthalmia, syndromic 12

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Baylor College of Medicine Research Center
• Matthew-Wood syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290216.3. 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
	RARB	NM_001290216.3		c.-332+17989C>A		intron	N/A	NP_001277145.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARB	ENST00000383772.9	TSL:5	c.-380+17989C>A		intron	N/A	ENSP00000373282.5
	RARB	ENST00000686715.1		c.-453+17989C>A		intron	N/A	ENSP00000510539.1
	RARB	ENST00000687353.1		c.-453+17989C>A		intron	N/A	ENSP00000508588.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17271 AN: 151964 Hom.: 1383 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0876

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0487

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0607

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.114 AC: 17287 AN: 152082 Hom.: 1388 Cov.: 32 AF XY: 0.115 AC XY: 8577 AN XY: 74368

African (AFR) AF: 0.202 AC: 8391 AN: 41476

American (AMR) AF: 0.0875 AC: 1337 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 402 AN: 3468

East Asian (EAS) AF: 0.294 AC: 1516 AN: 5160

South Asian (SAS) AF: 0.130 AC: 626 AN: 4822

European-Finnish (FIN) AF: 0.0487 AC: 517 AN: 10606

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0607 AC: 4127 AN: 67962

Other (OTH) AF: 0.104 AC: 219 AN: 2108

Alfa AF: 0.0858 Hom.: 1304

Bravo AF: 0.122

Asia WGS AF: 0.177 AC: 616 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.48
DANN	Benign	0.65
PhyloP100		-0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2362772; hg19: chr3-24918232;