rs708682

Variant names:

• chr15-61112996-G-A
• rs708682
• NM_134261.3:c.166+116057C>T

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+116057C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,230 control chromosomes in the GnomAD database, including 1,372 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 0.12 (1372 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.166+116057C>T		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+116057C>T		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17954 AN: 152112 Hom.: 1369 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.0484

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0962

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0759

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.118 AC: 17990 AN: 152230 Hom.: 1372 Cov.: 32 AF XY: 0.119 AC XY: 8856 AN XY: 74434

African (AFR) AF: 0.214 AC: 8870 AN: 41500

American (AMR) AF: 0.0875 AC: 1339 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0844 AC: 293 AN: 3470

East Asian (EAS) AF: 0.0489 AC: 253 AN: 5174

South Asian (SAS) AF: 0.149 AC: 717 AN: 4820

European-Finnish (FIN) AF: 0.0962 AC: 1021 AN: 10614

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0759 AC: 5162 AN: 68022

Other (OTH) AF: 0.116 AC: 245 AN: 2116

Alfa AF: 0.0881 Hom.: 1306

Bravo AF: 0.119

Asia WGS AF: 0.133 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.15
PhyloP100		-0.56
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: rs708682; hg19: chr15-61405195;