rs730754

Variant names:

• chr15-61159137-C-T
• rs730754
• NM_134261.3:c.166+69916G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134261.3(RORA):​c.166+69916G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 151,950 control chromosomes in the GnomAD database, including 25,211 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 0.57 (25211 hom., cov: 31)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 7 publications found

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]

RORA Gene-Disease associations (from GenCC):

• intellectual developmental disorder with or without epilepsy or cerebellar ataxia

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134261.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	NM_134261.3	MANE Select	c.166+69916G>A		intron	N/A	NP_599023.1	P35398-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	ENST00000335670.11	TSL:1 MANE Select	c.166+69916G>A		intron	N/A	ENSP00000335087.6	P35398-2
	RORA	ENST00000551975.5	TSL:3	n.79+69916G>A		intron	N/A	ENSP00000449482.1	H0YII6
	RORA	ENST00000557822.5	TSL:4	n.191+69916G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86605 AN: 151832 Hom.: 25192 Cov.: 31

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.570 AC: 86667 AN: 151950 Hom.: 25211 Cov.: 31 AF XY: 0.567 AC XY: 42145 AN XY: 74282

African (AFR) AF: 0.576 AC: 23877 AN: 41452

American (AMR) AF: 0.422 AC: 6447 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1865 AN: 3470

East Asian (EAS) AF: 0.406 AC: 2095 AN: 5154

South Asian (SAS) AF: 0.467 AC: 2245 AN: 4810

European-Finnish (FIN) AF: 0.654 AC: 6909 AN: 10568

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41191 AN: 67910

Other (OTH) AF: 0.530 AC: 1119 AN: 2110

Alfa AF: 0.587 Hom.: 3881

Bravo AF: 0.553

Asia WGS AF: 0.430 AC: 1494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.27
DANN	Benign	0.84
PhyloP100		-1.1
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: rs730754; hg19: chr15-61451336;