rs11632352

Variant names:

• chr15-61065667-C-T
• rs11632352
• NM_134261.3:c.166+163386G>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+163386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,050 control chromosomes in the GnomAD database, including 9,329 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 0.35 (9329 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia

LOC107984805 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.373 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	NM_134261.3	MANE Select	c.166+163386G>A		intron	N/A	NP_599023.1	P35398-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	ENST00000335670.11	TSL:1 MANE Select	c.166+163386G>A		intron	N/A	ENSP00000335087.6	P35398-2
	RORA	ENST00000551975.5	TSL:3	n.79+163386G>A		intron	N/A	ENSP00000449482.1	H0YII6
	RORA	ENST00000557822.5	TSL:4	n.191+163386G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52584 AN: 151932 Hom.: 9315 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.346 AC: 52621 AN: 152050 Hom.: 9329 Cov.: 32 AF XY: 0.349 AC XY: 25933 AN XY: 74326

African (AFR) AF: 0.279 AC: 11548 AN: 41460

American (AMR) AF: 0.361 AC: 5513 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1224 AN: 3470

East Asian (EAS) AF: 0.292 AC: 1511 AN: 5176

South Asian (SAS) AF: 0.330 AC: 1589 AN: 4818

European-Finnish (FIN) AF: 0.422 AC: 4462 AN: 10568

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25620 AN: 67956

Other (OTH) AF: 0.330 AC: 697 AN: 2112

Alfa AF: 0.358 Hom.: 1881

Bravo AF: 0.340

Asia WGS AF: 0.270 AC: 937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.8
DANN	Benign	0.48
PhyloP100		1.0
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: rs11632352; hg19: chr15-61357866;