rs2291296

Positions:

• chr3-25384391-G-A

Variant summary

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

The NR_134933.1(RARB-AS1):​n.282+255C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,214 control chromosomes in the GnomAD database, including 1,518 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 0.13 (1518 hom., cov: 32)
• Consequence: RARB-AS1 NR_134933.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419

Genes affected

RARB-AS1 (HGNC:):

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARB-AS1	NR_134933.1	n.282+255C>T		intron_variant, non_coding_transcript_variant
RARB	NM_001290216.3	c.179-76802G>A		intron_variant			NP_001277145.1
RARB	NM_001290300.2	c.28+43500G>A		intron_variant			NP_001277229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000383772.9	c.179-76802G>A		intron_variant		5		ENSP00000373282
RARB	ENST00000455576.2	c.179-76802G>A		intron_variant		4		ENSP00000508527
RARB	ENST00000686715.1	c.179-76802G>A		intron_variant				ENSP00000510539

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19103 AN: 152094 Hom.: 1516 Cov.: 32

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.126 AC: 19114 AN: 152214 Hom.: 1518 Cov.: 32 AF XY: 0.127 AC XY: 9449 AN XY: 74418

Gnomad4 AFR AF: 0.0394

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.129

Alfa AF: 0.141 Hom.: 222

Bravo AF: 0.110

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.31
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2291296; hg19: chr3-25425882;