rs7629902

Variant names:

• chr3-25459390-G-A
• rs7629902
• NM_000965.5:c.158-1803G>A

Variant summary

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

The NM_000965.5(RARB):​c.158-1803G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,224 control chromosomes in the GnomAD database, including 1,702 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 0.14 (1702 hom., cov: 32)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000965.5. 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_000965.5	MANE Select	c.158-1803G>A		intron	N/A	NP_000956.2
	RARB	NM_001290216.3		c.179-1803G>A		intron	N/A	NP_001277145.1	P10826-1
	RARB	NM_001290300.2		c.29-1803G>A		intron	N/A	NP_001277229.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARB	ENST00000330688.9	TSL:1 MANE Select	c.158-1803G>A		intron	N/A	ENSP00000332296.4	P10826-2
	RARB	ENST00000437042.7	TSL:1	c.-179-1803G>A		intron	N/A	ENSP00000398840.2	P10826-3
	RARB	ENST00000458646.2	TSL:1	c.-180+997G>A		intron	N/A	ENSP00000391391.1	P10826-3

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21667 AN: 152106 Hom.: 1700 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0971

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.142 AC: 21685 AN: 152224 Hom.: 1702 Cov.: 32 AF XY: 0.139 AC XY: 10359 AN XY: 74428

African (AFR) AF: 0.196 AC: 8123 AN: 41522

American (AMR) AF: 0.0970 AC: 1483 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5186

South Asian (SAS) AF: 0.109 AC: 524 AN: 4822

European-Finnish (FIN) AF: 0.112 AC: 1188 AN: 10602

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9537 AN: 68006

Other (OTH) AF: 0.129 AC: 272 AN: 2112

Alfa AF: 0.139 Hom.: 2497

Bravo AF: 0.141

Asia WGS AF: 0.0520 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.44
PhyloP100		-0.035
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7629902; hg19: chr3-25500881;