rs1730230

Positions:

• chr3-25578994-T-G

Variant summary

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

The NM_000965.5(RARB):​c.610-1552T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0853 in 152,254 control chromosomes in the GnomAD database, including 686 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 0.085 (686 hom., cov: 33)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARB	NM_000965.5	c.610-1552T>G		intron_variant		ENST00000330688.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARB	ENST00000330688.9	c.610-1552T>G		intron_variant		1	NM_000965.5	P1

Frequencies

GnomAD3 genomes AF: 0.0853 AC: 12972 AN: 152136 Hom.: 683 Cov.: 33

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0695

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

GnomAD4 genome AF: 0.0853 AC: 12983 AN: 152254 Hom.: 686 Cov.: 33 AF XY: 0.0851 AC XY: 6332 AN XY: 74436

Gnomad4 AFR AF: 0.0281

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0697

Alfa AF: 0.105 Hom.: 201

Bravo AF: 0.0839

Asia WGS AF: 0.0880 AC: 306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.33
DANN	Benign	0.36

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: rs1730230; hg19: chr3-25620485;