rs6780105

Variant names:

• chr3-25262214-C-G
• rs6780105
• NM_001290216.3:c.178+87639C>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.178+87639C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,160 control chromosomes in the GnomAD database, including 1,127 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 0.11 (1127 hom., cov: 32)
• Consequence: RARB NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 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.178+87639C>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.178+87639C>G		intron	N/A	ENSP00000373282.5
	RARB	ENST00000686715.1		c.178+87639C>G		intron	N/A	ENSP00000510539.1
	RARB	ENST00000687353.1		c.178+87639C>G		intron	N/A	ENSP00000508588.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16348 AN: 152042 Hom.: 1127 Cov.: 32

Gnomad AFR AF: 0.0308

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0858

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0420

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.107 AC: 16344 AN: 152160 Hom.: 1127 Cov.: 32 AF XY: 0.104 AC XY: 7702 AN XY: 74368

African (AFR) AF: 0.0307 AC: 1276 AN: 41540

American (AMR) AF: 0.0857 AC: 1309 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 362 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5182

South Asian (SAS) AF: 0.0421 AC: 203 AN: 4826

European-Finnish (FIN) AF: 0.157 AC: 1657 AN: 10584

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11200 AN: 67970

Other (OTH) AF: 0.109 AC: 231 AN: 2114

Alfa AF: 0.137 Hom.: 199

Bravo AF: 0.0985

Asia WGS AF: 0.0250 AC: 88 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.71
PhyloP100		-0.038
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: rs6780105; hg19: chr3-25303705;