rs3935025

Variant names:

• chr3-24714299-G-T
• rs3935025
• ENST00000687353.1:c.-587+26304G>T

Variant summary

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

The ENST00000687353.1(RARB):​c.-587+26304G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,816 control chromosomes in the GnomAD database, including 14,898 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 0.44 (14898 hom., cov: 32)
• Consequence: RARB ENST00000687353.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 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.-587+26304G>T		intron_variant	Intron 1 of 12			ENSP00000508588.1
RARB	ENST00000687676.1	c.-466+26304G>T		intron_variant	Intron 1 of 11			ENSP00000510313.1
RARB	ENST00000455576.2	c.-600+26304G>T		intron_variant	Intron 1 of 7	4		ENSP00000508527.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66333 AN: 151698 Hom.: 14881 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.437 AC: 66383 AN: 151816 Hom.: 14898 Cov.: 32 AF XY: 0.444 AC XY: 32936 AN XY: 74190

African (AFR) AF: 0.381 AC: 15772 AN: 41410

American (AMR) AF: 0.528 AC: 8050 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1579 AN: 3470

East Asian (EAS) AF: 0.740 AC: 3793 AN: 5126

South Asian (SAS) AF: 0.516 AC: 2490 AN: 4826

European-Finnish (FIN) AF: 0.475 AC: 5004 AN: 10536

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28283 AN: 67900

Other (OTH) AF: 0.442 AC: 931 AN: 2106

Alfa AF: 0.430 Hom.: 24636

Bravo AF: 0.439

Asia WGS AF: 0.580 AC: 2020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.72
PhyloP100		0.020

Splicing

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

Other links and lift over

dbSNP: rs3935025; hg19: chr3-24755790;