rs782918

Variant names:

• chr15-61107174-C-T
• rs782918
• NM_134261.3:c.166+121879G>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+121879G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,970 control chromosomes in the GnomAD database, including 5,439 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 0.26 (5439 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143
• Publications: 10 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.166+121879G>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+121879G>A		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39348 AN: 151850 Hom.: 5429 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.259 AC: 39392 AN: 151970 Hom.: 5439 Cov.: 32 AF XY: 0.263 AC XY: 19520 AN XY: 74298

African (AFR) AF: 0.335 AC: 13896 AN: 41420

American (AMR) AF: 0.181 AC: 2760 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3466

East Asian (EAS) AF: 0.219 AC: 1134 AN: 5170

South Asian (SAS) AF: 0.367 AC: 1766 AN: 4814

European-Finnish (FIN) AF: 0.309 AC: 3254 AN: 10536

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.221 AC: 15011 AN: 67972

Other (OTH) AF: 0.237 AC: 502 AN: 2114

Alfa AF: 0.229 Hom.: 12989

Bravo AF: 0.247

Asia WGS AF: 0.306 AC: 1064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.7
DANN	Benign	0.65
PhyloP100		-0.14
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: rs782918; hg19: chr15-61399373;