rs322668

Variant names:

• chr3-25302124-G-A
• rs322668
• NM_001290216.3:c.178+127549G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-25302124-G-A
• chr3-25302124-G-C
• chr3-25302124-G-T

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+127549G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,154 control chromosomes in the GnomAD database, including 42,573 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 0.74 (42573 hom., cov: 33)
• Consequence: RARB NM_001290216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• 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: 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARB	NM_001290216.3	c.178+127549G>A		intron_variant	Intron 4 of 10		NP_001277145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000383772.9	c.178+127549G>A		intron_variant	Intron 5 of 11	5		ENSP00000373282.5
RARB	ENST00000686715.1	c.178+127549G>A		intron_variant	Intron 5 of 11			ENSP00000510539.1
RARB	ENST00000687353.1	c.178+127549G>A		intron_variant	Intron 6 of 12			ENSP00000508588.1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 113025 AN: 152036 Hom.: 42530 Cov.: 33

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.744 AC: 113128 AN: 152154 Hom.: 42573 Cov.: 33 AF XY: 0.746 AC XY: 55481 AN XY: 74384

African (AFR) AF: 0.783 AC: 32496 AN: 41518

American (AMR) AF: 0.810 AC: 12376 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2470 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5175 AN: 5188

South Asian (SAS) AF: 0.870 AC: 4198 AN: 4826

European-Finnish (FIN) AF: 0.681 AC: 7183 AN: 10554

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46763 AN: 67990

Other (OTH) AF: 0.757 AC: 1598 AN: 2112

Alfa AF: 0.725 Hom.: 46754

Bravo AF: 0.754

Asia WGS AF: 0.926 AC: 3220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.64
PhyloP100		-0.21
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: rs322668; hg19: chr3-25343615;