3-25070680-C-T

Variant names:

• chr3-25070680-C-T
• rs993804
• NM_001290216.3:c.-280+10504C>T

Variant summary

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

The NM_001290216.3(RARB):​c.-280+10504C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,156 control chromosomes in the GnomAD database, including 42,655 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 0.75 (42655 hom., cov: 32)
• Consequence: RARB NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162
• Publications: 9 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: AD, AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Baylor College of Medicine Research Center, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 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.-280+10504C>T		intron	N/A	NP_001277145.1	P10826-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARB	ENST00000383772.9	TSL:5	c.-328+10504C>T		intron	N/A	ENSP00000373282.5	P10826-1
	RARB	ENST00000686715.1		c.-400-5483C>T		intron	N/A	ENSP00000510539.1	P10826-1
	RARB	ENST00000687353.1		c.-400-5483C>T		intron	N/A	ENSP00000508588.1	P10826-1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113605 AN: 152038 Hom.: 42636 Cov.: 32

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.908

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.747 AC: 113668 AN: 152156 Hom.: 42655 Cov.: 32 AF XY: 0.750 AC XY: 55771 AN XY: 74386

African (AFR) AF: 0.716 AC: 29711 AN: 41506

American (AMR) AF: 0.743 AC: 11358 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2648 AN: 3472

East Asian (EAS) AF: 0.821 AC: 4258 AN: 5186

South Asian (SAS) AF: 0.703 AC: 3389 AN: 4820

European-Finnish (FIN) AF: 0.769 AC: 8129 AN: 10576

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51575 AN: 67982

Other (OTH) AF: 0.737 AC: 1558 AN: 2114

Alfa AF: 0.752 Hom.: 104564

Bravo AF: 0.741

Asia WGS AF: 0.725 AC: 2519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs993804; hg19: chr3-25112171;