rs10510550

Variant names:

• chr3-24884963-T-C
• rs10510550
• NM_001290216.3:c.-332+26211T>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+26211T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.059 in 152,206 control chromosomes in the GnomAD database, including 415 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 0.059 (415 hom., cov: 32)
• Consequence: RARB NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARB	NM_001290216.3	c.-332+26211T>C		intron_variant	Intron 2 of 10		NP_001277145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000383772.9	c.-380+26211T>C		intron_variant	Intron 2 of 11	5		ENSP00000373282.5
RARB	ENST00000686715.1	c.-453+26211T>C		intron_variant	Intron 2 of 11			ENSP00000510539.1
RARB	ENST00000687353.1	c.-453+26211T>C		intron_variant	Intron 3 of 12			ENSP00000508588.1

Frequencies

GnomAD3 genomes AF: 0.0591 AC: 8983 AN: 152088 Hom.: 414 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0454

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0325

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0506

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

GnomAD4 genome AF: 0.0590 AC: 8982 AN: 152206 Hom.: 415 Cov.: 32 AF XY: 0.0608 AC XY: 4521 AN XY: 74414

African (AFR) AF: 0.109 AC: 4532 AN: 41524

American (AMR) AF: 0.0453 AC: 692 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3468

East Asian (EAS) AF: 0.147 AC: 762 AN: 5172

South Asian (SAS) AF: 0.103 AC: 498 AN: 4826

European-Finnish (FIN) AF: 0.0325 AC: 345 AN: 10608

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0275 AC: 1871 AN: 68016

Other (OTH) AF: 0.0501 AC: 106 AN: 2116

Alfa AF: 0.0457 Hom.: 35

Bravo AF: 0.0627

Asia WGS AF: 0.0840 AC: 293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.66
PhyloP100		-0.71

Splicing

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

Other links and lift over

dbSNP: rs10510550; hg19: chr3-24926454;