3-24716877-G-A

Variant names:

• chr3-24716877-G-A
• rs4858125
• ENST00000687353.1:c.-587+28882G>A

Variant summary

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

The ENST00000455576.2(RARB):​c.-600+28882G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,666 control chromosomes in the GnomAD database, including 22,658 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 (22658 hom., cov: 30)
• Consequence: RARB ENST00000455576.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000455576.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARB	ENST00000687353.1		c.-587+28882G>A		intron	N/A	ENSP00000508588.1
	RARB	ENST00000687676.1		c.-466+28882G>A		intron	N/A	ENSP00000510313.1
	RARB	ENST00000455576.2	TSL:4	c.-600+28882G>A		intron	N/A	ENSP00000508527.1

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81741 AN: 151548 Hom.: 22630 Cov.: 30

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.540 AC: 81825 AN: 151666 Hom.: 22658 Cov.: 30 AF XY: 0.547 AC XY: 40498 AN XY: 74062

African (AFR) AF: 0.545 AC: 22550 AN: 41362

American (AMR) AF: 0.614 AC: 9363 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1370 AN: 3470

East Asian (EAS) AF: 0.859 AC: 4398 AN: 5118

South Asian (SAS) AF: 0.695 AC: 3337 AN: 4804

European-Finnish (FIN) AF: 0.512 AC: 5373 AN: 10498

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33789 AN: 67856

Other (OTH) AF: 0.529 AC: 1114 AN: 2106

Alfa AF: 0.513 Hom.: 37570

Bravo AF: 0.543

Asia WGS AF: 0.755 AC: 2630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.43
DANN	Benign	0.36
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs4858125; hg19: chr3-24758368;