rs1368262

Variant names:

• chr3-25479074-A-G
• rs1368262
• NM_000965.5:c.306+17733A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-25479074-A-G
• chr3-25479074-A-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000965.5(RARB):​c.306+17733A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,000 control chromosomes in the GnomAD database, including 7,948 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 0.29 (7948 hom., cov: 32)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARB	NM_000965.5	c.306+17733A>G		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.306+17733A>G		intron_variant	Intron 2 of 7	1	NM_000965.5	ENSP00000332296.4

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43396 AN: 151882 Hom.: 7930 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.286 AC: 43469 AN: 152000 Hom.: 7948 Cov.: 32 AF XY: 0.283 AC XY: 21036 AN XY: 74320

African (AFR) AF: 0.528 AC: 21900 AN: 41442

American (AMR) AF: 0.213 AC: 3251 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3472

East Asian (EAS) AF: 0.221 AC: 1141 AN: 5158

South Asian (SAS) AF: 0.213 AC: 1026 AN: 4810

European-Finnish (FIN) AF: 0.184 AC: 1942 AN: 10564

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12670 AN: 67958

Other (OTH) AF: 0.261 AC: 552 AN: 2112

Alfa AF: 0.222 Hom.: 3331

Bravo AF: 0.298

Asia WGS AF: 0.246 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.2
DANN	Benign	0.80
PhyloP100		0.25
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: rs1368262; hg19: chr3-25520565;