rs11271404

Positions:

• chr3-25467503-TACAATCATAGCAAGCCAACGCCACTTATCCAGTGAACCA-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000965.5(RARB):​c.306+6163_306+6201del variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (16476 hom., cov: 0)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARB	NM_000965.5	c.306+6163_306+6201del		intron_variant		ENST00000330688.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARB	ENST00000330688.9	c.306+6163_306+6201del		intron_variant		1	NM_000965.5	P1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70210 AN: 151138 Hom.: 16460 Cov.: 0

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.442

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.465 AC: 70269 AN: 151250 Hom.: 16476 Cov.: 0 AF XY: 0.467 AC XY: 34478 AN XY: 73862

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.449

Alfa AF: 0.468 Hom.: 1784

Asia WGS AF: 0.581 AC: 2019 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11271404; hg19: chr3-25508994;