3-25023407-C-G

Variant names:

• chr3-25023407-C-G
• rs10865802
• NM_001290216.3:c.-331-36718C>G

Variant summary

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

The NM_001290216.3(RARB):​c.-331-36718C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 151,964 control chromosomes in the GnomAD database, including 10,845 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 0.37 (10845 hom., cov: 32)
• Consequence: RARB NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.521
• 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 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARB	NM_001290216.3		c.-331-36718C>G		intron	N/A	NP_001277145.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARB	ENST00000383772.9	TSL:5	c.-379-36718C>G		intron	N/A	ENSP00000373282.5
	RARB	ENST00000686715.1		c.-452-36718C>G		intron	N/A	ENSP00000510539.1
	RARB	ENST00000687353.1		c.-452-36718C>G		intron	N/A	ENSP00000508588.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56764 AN: 151846 Hom.: 10826 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.374 AC: 56820 AN: 151964 Hom.: 10845 Cov.: 32 AF XY: 0.369 AC XY: 27447 AN XY: 74294

African (AFR) AF: 0.403 AC: 16669 AN: 41404

American (AMR) AF: 0.286 AC: 4361 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1058 AN: 3472

East Asian (EAS) AF: 0.261 AC: 1351 AN: 5180

South Asian (SAS) AF: 0.340 AC: 1637 AN: 4818

European-Finnish (FIN) AF: 0.342 AC: 3609 AN: 10550

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.395 AC: 26856 AN: 67964

Other (OTH) AF: 0.364 AC: 769 AN: 2112

Alfa AF: 0.212 Hom.: 424

Bravo AF: 0.374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
DANN	Benign	0.50
PhyloP100		0.52

Splicing

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

Other links and lift over

dbSNP: rs10865802; hg19: chr3-25064898;