rs4858125

chr3-24716877-G-Achr3-24716877-G-Cchr3-24716877-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000687353.1(RARB):c.-587+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 ENST00000687353.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARB	ENST00000455576.2	c.-600+28882G>A		intron_variant		4
RARB	ENST00000687353.1	c.-587+28882G>A		intron_variant
RARB	ENST00000687676.1	c.-466+28882G>A		intron_variant

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

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.859

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.529

Alfa AF: 0.507 Hom.: 26131

Bravo AF: 0.543

Asia WGS AF: 0.755 AC: 2630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.43
Dann	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4858125; hg19: chr3-24758368;