rs2363523

Variant names:

• chr3-24923796-T-A
• rs2363523
• NM_001290216.3:c.-332+65044T>A

Your query was ambiguous. Multiple possible variants found:

• chr3-24923796-T-A
• chr3-24923796-T-G

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+65044T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 151,982 control chromosomes in the GnomAD database, including 20,484 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 0.51 (20484 hom., cov: 32)
• Consequence: RARB NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARB	NM_001290216.3	c.-332+65044T>A		intron_variant	Intron 2 of 10		NP_001277145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000383772.9	c.-380+65044T>A		intron_variant	Intron 2 of 11	5		ENSP00000373282.5
RARB	ENST00000686715.1	c.-453+65044T>A		intron_variant	Intron 2 of 11			ENSP00000510539.1
RARB	ENST00000687353.1	c.-453+65044T>A		intron_variant	Intron 3 of 12			ENSP00000508588.1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77113 AN: 151866 Hom.: 20452 Cov.: 32

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.508 AC: 77195 AN: 151982 Hom.: 20484 Cov.: 32 AF XY: 0.505 AC XY: 37535 AN XY: 74280

African (AFR) AF: 0.606 AC: 25099 AN: 41446

American (AMR) AF: 0.342 AC: 5219 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1368 AN: 3472

East Asian (EAS) AF: 0.717 AC: 3695 AN: 5154

South Asian (SAS) AF: 0.570 AC: 2745 AN: 4818

European-Finnish (FIN) AF: 0.479 AC: 5065 AN: 10572

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.477 AC: 32402 AN: 67940

Other (OTH) AF: 0.468 AC: 989 AN: 2114

Alfa AF: 0.484 Hom.: 2256

Bravo AF: 0.503

Asia WGS AF: 0.617 AC: 2144 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.57
DANN	Benign	0.42
PhyloP100		-0.46

Splicing

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

Other links and lift over

dbSNP: rs2363523; hg19: chr3-24965287;