rs1483856

Variant names:

• chr3-25432454-G-T
• rs1483856
• NM_000965.5:c.157+3566G>T

Variant summary

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

The NM_000965.5(RARB):​c.157+3566G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.896 in 152,232 control chromosomes in the GnomAD database, including 61,200 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 0.90 (61200 hom., cov: 32)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 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.157+3566G>T		intron	N/A	NP_000956.2
	RARB	NM_001290216.3		c.179-28739G>T		intron	N/A	NP_001277145.1	P10826-1
	RARB	NM_001290300.2		c.29-28739G>T		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.157+3566G>T		intron	N/A	ENSP00000332296.4	P10826-2
	RARB	ENST00000437042.7	TSL:1	c.-180+3923G>T		intron	N/A	ENSP00000398840.2	P10826-3
	RARB	ENST00000383772.9	TSL:5	c.179-28739G>T		intron	N/A	ENSP00000373282.5	P10826-1

Frequencies

GnomAD3 genomes AF: 0.896 AC: 136355 AN: 152114 Hom.: 61157 Cov.: 32

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.926

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.869

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

GnomAD4 genome AF: 0.896 AC: 136455 AN: 152232 Hom.: 61200 Cov.: 32 AF XY: 0.897 AC XY: 66745 AN XY: 74436

African (AFR) AF: 0.895 AC: 37187 AN: 41558

American (AMR) AF: 0.914 AC: 13980 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 3140 AN: 3470

East Asian (EAS) AF: 0.995 AC: 5152 AN: 5178

South Asian (SAS) AF: 0.926 AC: 4460 AN: 4818

European-Finnish (FIN) AF: 0.860 AC: 9114 AN: 10602

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.889 AC: 60451 AN: 67996

Other (OTH) AF: 0.871 AC: 1834 AN: 2106

Alfa AF: 0.899 Hom.: 25337

Bravo AF: 0.899

Asia WGS AF: 0.960 AC: 3335 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.50
PhyloP100		-0.32
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: rs1483856; hg19: chr3-25473945;