rs6794719

chr3-24761048-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARB	ENST00000455576.2	c.-599-1192A>T		intron_variant		4
RARB	ENST00000687353.1	c.-586-1192A>T		intron_variant
RARB	ENST00000687676.1	c.-465-1192A>T		intron_variant

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

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.394

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6794719; hg19: chr3-24802539;