rs2433025

Variant names:

• chr15-60715469-A-G
• rs2433025
• NM_134261.3:c.167-36783T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-60715469-A-G
• chr15-60715469-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134261.3(RORA):​c.167-36783T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,020 control chromosomes in the GnomAD database, including 33,748 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 0.66 (33748 hom., cov: 33)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.392
• Publications: 6 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 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.167-36783T>C		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.167-36783T>C		intron	N/A	ENSP00000335087.6	P35398-2
	RORA	ENST00000551975.5	TSL:3	n.80-36783T>C		intron	N/A	ENSP00000449482.1	H0YII6
	RORA	ENST00000557822.5	TSL:4	n.192-36783T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100873 AN: 151902 Hom.: 33702 Cov.: 33

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.676

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.664 AC: 100984 AN: 152020 Hom.: 33748 Cov.: 33 AF XY: 0.669 AC XY: 49705 AN XY: 74286

African (AFR) AF: 0.730 AC: 30308 AN: 41490

American (AMR) AF: 0.693 AC: 10599 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2335 AN: 3468

East Asian (EAS) AF: 0.731 AC: 3785 AN: 5176

South Asian (SAS) AF: 0.729 AC: 3509 AN: 4812

European-Finnish (FIN) AF: 0.672 AC: 7070 AN: 10524

Middle Eastern (MID) AF: 0.676 AC: 196 AN: 290

European-Non Finnish (NFE) AF: 0.608 AC: 41325 AN: 67952

Other (OTH) AF: 0.701 AC: 1481 AN: 2112

Alfa AF: 0.628 Hom.: 116053

Bravo AF: 0.670

Asia WGS AF: 0.739 AC: 2569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.5
DANN	Benign	0.46
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2433025; hg19: chr15-61007668;