rs6782425

Positions:

• chr3-25588575-G-A

Variant summary

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

The NM_000965.5(RARB):​c.787-4928G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,000 control chromosomes in the GnomAD database, including 6,700 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 0.28 (6700 hom., cov: 32)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARB	NM_000965.5	c.787-4928G>A		intron_variant		ENST00000330688.9	NP_000956.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000330688.9	c.787-4928G>A		intron_variant		1	NM_000965.5	ENSP00000332296.4

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42510 AN: 151882 Hom.: 6682 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.280 AC: 42574 AN: 152000 Hom.: 6700 Cov.: 32 AF XY: 0.280 AC XY: 20833 AN XY: 74286

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.247

Alfa AF: 0.225 Hom.: 8381

Bravo AF: 0.292

Asia WGS AF: 0.306 AC: 1061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.14
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6782425; hg19: chr3-25630066;