rs12591650

Positions:

• chr15-60768508-A-G
• chr15-60768508-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134261.3(RORA):​c.167-89822T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,174 control chromosomes in the GnomAD database, including 2,228 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 0.15 (2228 hom., cov: 33)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORA	NM_134261.3	c.167-89822T>C		intron_variant		ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1751-89822T>C		intron_variant			XP_047288884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.167-89822T>C		intron_variant		1	NM_134261.3	ENSP00000335087

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23229 AN: 152056 Hom.: 2231 Cov.: 33

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.153 AC: 23225 AN: 152174 Hom.: 2228 Cov.: 33 AF XY: 0.157 AC XY: 11699 AN XY: 74396

Gnomad4 AFR AF: 0.0817

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.189

Alfa AF: 0.161 Hom.: 4466

Bravo AF: 0.154

Asia WGS AF: 0.300 AC: 1045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.9
DANN	Benign	0.70

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: rs12591650; hg19: chr15-61060707;