rs2291296

Variant names:

• chr3-25384391-G-A
• rs2291296
• NM_001290216.3:c.179-76802G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290216.3(RARB):​c.179-76802G>A variant causes a intron 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 NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419
• Publications: 3 publications found

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-AS1 (HGNC:):

RARB-AS1 (HGNC:54077): (RARB antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RARB	NM_001290216.3	c.179-76802G>A		intron_variant	Intron 4 of 10		NP_001277145.1
RARB	NM_001290300.2	c.28+43500G>A		intron_variant	Intron 1 of 7		NP_001277229.1
RARB-AS1	NR_134933.1	n.282+255C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000383772.9	c.179-76802G>A		intron_variant	Intron 5 of 11	5		ENSP00000373282.5
RARB	ENST00000686715.1	c.179-76802G>A		intron_variant	Intron 5 of 11			ENSP00000510539.1
RARB	ENST00000687353.1	c.179-76802G>A		intron_variant	Intron 6 of 12			ENSP00000508588.1

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

African (AFR) AF: 0.0394 AC: 1636 AN: 41540

American (AMR) AF: 0.102 AC: 1563 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3472

East Asian (EAS) AF: 0.101 AC: 522 AN: 5182

South Asian (SAS) AF: 0.201 AC: 970 AN: 4822

European-Finnish (FIN) AF: 0.220 AC: 2328 AN: 10596

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11339 AN: 67988

Other (OTH) AF: 0.129 AC: 272 AN: 2114

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
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2291296; hg19: chr3-25425882;