15-61102033-A-G

Variant names:

• chr15-61102033-A-G
• rs893287
• NM_134261.3:c.166+127020T>C

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+127020T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,826 control chromosomes in the GnomAD database, including 28,952 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 0.62 (28952 hom., cov: 30)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.688 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+127020T>C		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+127020T>C		intron	N/A	ENSP00000335087.6
	RORA	ENST00000551975.5	TSL:3	n.79+127020T>C		intron	N/A	ENSP00000449482.1
	RORA	ENST00000557822.5	TSL:4	n.191+127020T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93340 AN: 151708 Hom.: 28919 Cov.: 30

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.615 AC: 93418 AN: 151826 Hom.: 28952 Cov.: 30 AF XY: 0.619 AC XY: 45929 AN XY: 74170

African (AFR) AF: 0.587 AC: 24271 AN: 41374

American (AMR) AF: 0.699 AC: 10676 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2143 AN: 3464

East Asian (EAS) AF: 0.651 AC: 3351 AN: 5144

South Asian (SAS) AF: 0.550 AC: 2643 AN: 4802

European-Finnish (FIN) AF: 0.650 AC: 6843 AN: 10530

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41413 AN: 67934

Other (OTH) AF: 0.636 AC: 1340 AN: 2106

Alfa AF: 0.609 Hom.: 10388

Bravo AF: 0.622

Asia WGS AF: 0.640 AC: 2229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.0
DANN	Benign	0.35
PhyloP100		0.43
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: rs893287; hg19: chr15-61394232; COSMIC: COSV59546573;