rs8027829

Variant names:

• chr15-60881672-A-G
• rs8027829
• NM_134261.3:c.167-202986T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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 rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.167-202986T>C		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1751-202986T>C		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.167-202986T>C		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

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

African (AFR) AF: 0.364 AC: 15106 AN: 41456

American (AMR) AF: 0.429 AC: 6539 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1863 AN: 3468

East Asian (EAS) AF: 0.206 AC: 1062 AN: 5156

South Asian (SAS) AF: 0.505 AC: 2434 AN: 4818

European-Finnish (FIN) AF: 0.640 AC: 6745 AN: 10540

Middle Eastern (MID) AF: 0.472 AC: 137 AN: 290

European-Non Finnish (NFE) AF: 0.591 AC: 40168 AN: 67960

Other (OTH) AF: 0.471 AC: 995 AN: 2112

Alfa AF: 0.549 Hom.: 36620

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
PhyloP100		0.38
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: rs8027829; hg19: chr15-61173871;