rs782925

Variant names:

• chr15-61111225-C-T
• rs782925
• NM_134261.3:c.166+117828G>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+117828G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,020 control chromosomes in the GnomAD database, including 4,934 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 0.25 (4934 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.444
• Publications: 6 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

LOC107984805 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.166+117828G>A		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.166+117828G>A		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37699 AN: 151902 Hom.: 4920 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.248 AC: 37753 AN: 152020 Hom.: 4934 Cov.: 32 AF XY: 0.251 AC XY: 18678 AN XY: 74314

African (AFR) AF: 0.316 AC: 13108 AN: 41430

American (AMR) AF: 0.174 AC: 2659 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3470

East Asian (EAS) AF: 0.217 AC: 1123 AN: 5170

South Asian (SAS) AF: 0.359 AC: 1729 AN: 4814

European-Finnish (FIN) AF: 0.288 AC: 3042 AN: 10550

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14548 AN: 67988

Other (OTH) AF: 0.234 AC: 494 AN: 2110

Alfa AF: 0.227 Hom.: 723

Bravo AF: 0.237

Asia WGS AF: 0.309 AC: 1074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.43
DANN	Benign	0.41
PhyloP100		-0.44
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: rs782925; hg19: chr15-61403424;