rs1299407

Variant names:

• chr3-25490433-G-A
• rs1299407
• NM_000965.5:c.307-10749G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-25490433-G-A
• chr3-25490433-G-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.307-10749G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,022 control chromosomes in the GnomAD database, including 22,666 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 0.53 (22666 hom., cov: 33)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARB	NM_000965.5	c.307-10749G>A		intron_variant	Intron 2 of 7	ENST00000330688.9	NP_000956.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000330688.9	c.307-10749G>A		intron_variant	Intron 2 of 7	1	NM_000965.5	ENSP00000332296.4

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79896 AN: 151904 Hom.: 22622 Cov.: 33

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.526 AC: 79991 AN: 152022 Hom.: 22666 Cov.: 33 AF XY: 0.524 AC XY: 38951 AN XY: 74318

African (AFR) AF: 0.746 AC: 30935 AN: 41470

American (AMR) AF: 0.519 AC: 7926 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1655 AN: 3466

East Asian (EAS) AF: 0.554 AC: 2863 AN: 5166

South Asian (SAS) AF: 0.362 AC: 1744 AN: 4820

European-Finnish (FIN) AF: 0.444 AC: 4690 AN: 10566

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28711 AN: 67960

Other (OTH) AF: 0.523 AC: 1102 AN: 2108

Alfa AF: 0.443 Hom.: 12122

Bravo AF: 0.547

Asia WGS AF: 0.495 AC: 1721 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.75
PhyloP100		0.24
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: rs1299407; hg19: chr3-25531924;