rs11631432

Variant names:

• chr15-60882149-C-T
• rs11631432
• NM_134261.3:c.167-203463G>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.167-203463G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 152,062 control chromosomes in the GnomAD database, including 15,749 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 0.43 (15749 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515
• 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 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.167-203463G>A		intron	N/A	NP_599023.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	ENST00000335670.11	TSL:1 MANE Select	c.167-203463G>A		intron	N/A	ENSP00000335087.6
	RORA	ENST00000551975.5	TSL:3	n.80-203463G>A		intron	N/A	ENSP00000449482.1
	RORA	ENST00000557822.5	TSL:4	n.192-203463G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65593 AN: 151942 Hom.: 15748 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.432 AC: 65616 AN: 152062 Hom.: 15749 Cov.: 32 AF XY: 0.439 AC XY: 32625 AN XY: 74332

African (AFR) AF: 0.207 AC: 8587 AN: 41480

American (AMR) AF: 0.542 AC: 8273 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2097 AN: 3470

East Asian (EAS) AF: 0.570 AC: 2944 AN: 5164

South Asian (SAS) AF: 0.488 AC: 2354 AN: 4820

European-Finnish (FIN) AF: 0.562 AC: 5937 AN: 10560

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33817 AN: 67998

Other (OTH) AF: 0.452 AC: 950 AN: 2100

Alfa AF: 0.479 Hom.: 30892

Bravo AF: 0.424

Asia WGS AF: 0.490 AC: 1705 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.5
DANN	Benign	0.84
PhyloP100		-0.52
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: rs11631432; hg19: chr15-61174348;