rs1299407

Positions:

• chr3-25490433-G-A
• chr3-25490433-G-T

Variant summary

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

The NM_000965.5(RARB):​c.307-10749G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,022 control chromosomes in the GnomAD database, including 22,666 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 0.53 (22666 hom., cov: 33)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARB	NM_000965.5	c.307-10749G>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.307-10749G>A		intron_variant		1	NM_000965.5	ENSP00000332296	P1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79896 AN: 151904 Hom.: 22622 Cov.: 33

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.526 AC: 79991 AN: 152022 Hom.: 22666 Cov.: 33 AF XY: 0.524 AC XY: 38951 AN XY: 74318

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.523

Alfa AF: 0.435 Hom.: 9626

Bravo AF: 0.547

Asia WGS AF: 0.495 AC: 1721 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.75

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: rs1299407; hg19: chr3-25531924;