3-24886049-G-C

Variant names:

• chr3-24886049-G-C
• rs7340729
• NM_001290216.3:c.-332+27297G>C

Variant summary

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

The NM_001290216.3(RARB):​c.-332+27297G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0763 in 152,150 control chromosomes in the GnomAD database, including 955 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 0.076 (955 hom., cov: 32)
• Consequence: RARB NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 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.-332+27297G>C		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.-380+27297G>C		intron	N/A	ENSP00000373282.5
	RARB	ENST00000686715.1		c.-453+27297G>C		intron	N/A	ENSP00000510539.1
	RARB	ENST00000687353.1		c.-453+27297G>C		intron	N/A	ENSP00000508588.1

Frequencies

GnomAD3 genomes AF: 0.0761 AC: 11573 AN: 152032 Hom.: 952 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.0338

Gnomad FIN AF: 0.00142

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.0874

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

GnomAD4 genome AF: 0.0763 AC: 11607 AN: 152150 Hom.: 955 Cov.: 32 AF XY: 0.0772 AC XY: 5738 AN XY: 74354

African (AFR) AF: 0.165 AC: 6837 AN: 41498

American (AMR) AF: 0.104 AC: 1584 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0585 AC: 203 AN: 3470

East Asian (EAS) AF: 0.326 AC: 1679 AN: 5156

South Asian (SAS) AF: 0.0335 AC: 161 AN: 4812

European-Finnish (FIN) AF: 0.00142 AC: 15 AN: 10588

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0130 AC: 887 AN: 68026

Other (OTH) AF: 0.0879 AC: 186 AN: 2116

Alfa AF: 0.00149 Hom.: 0

Bravo AF: 0.0917

Asia WGS AF: 0.155 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.51
PhyloP100		0.29

Splicing

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

Other links and lift over

dbSNP: rs7340729; hg19: chr3-24927540;