ENST00000687353.1:c.-586-1192A>T

Variant names:

• chr3-24761048-A-T
• rs6794719
• ENST00000687353.1:c.-586-1192A>T

Variant summary

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

The ENST00000687353.1(RARB):​c.-586-1192A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 151,902 control chromosomes in the GnomAD database, including 11,186 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 0.37 (11186 hom., cov: 31)
• Consequence: RARB ENST00000687353.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000687353.1	c.-586-1192A>T		intron_variant	Intron 1 of 12			ENSP00000508588.1
RARB	ENST00000687676.1	c.-465-1192A>T		intron_variant	Intron 1 of 11			ENSP00000510313.1
RARB	ENST00000455576.2	c.-599-1192A>T		intron_variant	Intron 1 of 7	4		ENSP00000508527.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55913 AN: 151784 Hom.: 11171 Cov.: 31

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.368 AC: 55974 AN: 151902 Hom.: 11186 Cov.: 31 AF XY: 0.364 AC XY: 26999 AN XY: 74240

African (AFR) AF: 0.529 AC: 21878 AN: 41390

American (AMR) AF: 0.309 AC: 4721 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1202 AN: 3470

East Asian (EAS) AF: 0.283 AC: 1451 AN: 5126

South Asian (SAS) AF: 0.364 AC: 1749 AN: 4804

European-Finnish (FIN) AF: 0.210 AC: 2218 AN: 10578

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21427 AN: 67962

Other (OTH) AF: 0.394 AC: 832 AN: 2112

Alfa AF: 0.334 Hom.: 1256

Bravo AF: 0.382

Asia WGS AF: 0.352 AC: 1223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.81
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs6794719; hg19: chr3-24802539;