3-25308047-G-A

Variant names:

• chr3-25308047-G-A
• rs322695
• NM_001290216.3:c.178+133472G>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.178+133472G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,114 control chromosomes in the GnomAD database, including 1,655 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 (1655 hom., cov: 32)
• Consequence: RARB NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 8 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 Gene-Disease associations (from GenCC):

• microphthalmia, syndromic 12

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Baylor College of Medicine Research Center
• Matthew-Wood syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290216.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARB	NM_001290216.3		c.178+133472G>A		intron	N/A	NP_001277145.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARB	ENST00000383772.9	TSL:5	c.178+133472G>A		intron	N/A	ENSP00000373282.5
	RARB	ENST00000686715.1		c.178+133472G>A		intron	N/A	ENSP00000510539.1
	RARB	ENST00000687353.1		c.178+133472G>A		intron	N/A	ENSP00000508588.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20399 AN: 151996 Hom.: 1647 Cov.: 32

Gnomad AFR AF: 0.0618

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.0548

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.134 AC: 20416 AN: 152114 Hom.: 1655 Cov.: 32 AF XY: 0.138 AC XY: 10241 AN XY: 74330

African (AFR) AF: 0.0617 AC: 2563 AN: 41524

American (AMR) AF: 0.111 AC: 1700 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3468

East Asian (EAS) AF: 0.0547 AC: 284 AN: 5188

South Asian (SAS) AF: 0.250 AC: 1201 AN: 4810

European-Finnish (FIN) AF: 0.235 AC: 2479 AN: 10548

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11362 AN: 67988

Other (OTH) AF: 0.141 AC: 297 AN: 2112

Alfa AF: 0.155 Hom.: 8943

Bravo AF: 0.118

Asia WGS AF: 0.170 AC: 591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.65
DANN	Benign	0.33
PhyloP100		0.011
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: rs322695; hg19: chr3-25349538;