rs873961

Variant names:

• chr15-61056005-C-T
• rs873961
• NM_134261.3:c.166+173048G>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+173048G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,014 control chromosomes in the GnomAD database, including 9,044 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 0.34 (9044 hom., cov: 33)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• 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)

LOC107984805 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134261.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	NM_134261.3	MANE Select	c.166+173048G>A		intron	N/A	NP_599023.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	ENST00000335670.11	TSL:1 MANE Select	c.166+173048G>A		intron	N/A	ENSP00000335087.6
	RORA	ENST00000551975.5	TSL:3	n.79+173048G>A		intron	N/A	ENSP00000449482.1
	RORA	ENST00000557822.5	TSL:4	n.191+173048G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52196 AN: 151896 Hom.: 9027 Cov.: 33

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.344 AC: 52257 AN: 152014 Hom.: 9044 Cov.: 33 AF XY: 0.343 AC XY: 25481 AN XY: 74310

African (AFR) AF: 0.300 AC: 12445 AN: 41468

American (AMR) AF: 0.358 AC: 5469 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1214 AN: 3466

East Asian (EAS) AF: 0.229 AC: 1185 AN: 5166

South Asian (SAS) AF: 0.313 AC: 1504 AN: 4804

European-Finnish (FIN) AF: 0.372 AC: 3921 AN: 10550

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25389 AN: 67966

Other (OTH) AF: 0.333 AC: 704 AN: 2114

Alfa AF: 0.363 Hom.: 15916

Bravo AF: 0.343

Asia WGS AF: 0.237 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.62
PhyloP100		-0.37
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: rs873961; hg19: chr15-61348204;