rs1020729

Variant names:

• chr15-60752873-T-C
• rs1020729
• NM_134261.3:c.167-74187A>G

Variant summary

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

The NM_134261.3(RORA):​c.167-74187A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,038 control chromosomes in the GnomAD database, including 27,943 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 0.60 (27943 hom., cov: 31)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• Publications: 5 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.167-74187A>G		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1751-74187A>G		intron_variant	Intron 1 of 10		XP_047288884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.167-74187A>G		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91546 AN: 151920 Hom.: 27926 Cov.: 31

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.603 AC: 91609 AN: 152038 Hom.: 27943 Cov.: 31 AF XY: 0.603 AC XY: 44839 AN XY: 74308

African (AFR) AF: 0.528 AC: 21870 AN: 41444

American (AMR) AF: 0.617 AC: 9428 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2187 AN: 3470

East Asian (EAS) AF: 0.435 AC: 2257 AN: 5188

South Asian (SAS) AF: 0.695 AC: 3347 AN: 4814

European-Finnish (FIN) AF: 0.644 AC: 6809 AN: 10566

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.643 AC: 43684 AN: 67956

Other (OTH) AF: 0.574 AC: 1214 AN: 2114

Alfa AF: 0.628 Hom.: 3894

Bravo AF: 0.592

Asia WGS AF: 0.576 AC: 1997 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	16
DANN	Benign	0.78
PhyloP100		-0.012
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1020729; hg19: chr15-61045072;