rs8027829

Positions:

• chr15-60881672-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_134261.3(RORA):​c.167-202986T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,972 control chromosomes in the GnomAD database, including 20,042 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 0.50 (20042 hom., cov: 31)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378

Genes affected

RORA (HGNC:10258): (RAR related orphan receptor A) The protein encoded by this gene is a member of the NR1 subfamily of nuclear hormone receptors. It can bind as a monomer or as a homodimer to hormone response elements upstream of several genes to enhance the expression of those genes. The encoded protein has been shown to interact with NM23-2, a nucleoside diphosphate kinase involved in organogenesis and differentiation, as well as with NM23-1, the product of a tumor metastasis suppressor candidate gene. Also, it has been shown to aid in the transcriptional regulation of some genes involved in circadian rhythm. Four transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RORA	NM_134261.3	c.167-202986T>C		intron_variant		ENST00000335670.11
RORA	XM_047432928.1	c.-1751-202986T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORA	ENST00000335670.11	c.167-202986T>C		intron_variant		1	NM_134261.3

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75686 AN: 151854 Hom.: 20044 Cov.: 31

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.498 AC: 75702 AN: 151972 Hom.: 20042 Cov.: 31 AF XY: 0.498 AC XY: 37016 AN XY: 74276

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.471

Alfa AF: 0.556 Hom.: 29014

Bravo AF: 0.469

Asia WGS AF: 0.336 AC: 1171 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.2
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs8027829; hg19: chr15-61173871;