NM_134261.3:c.167-174986T>C

Variant names:

• chr15-60853672-A-G
• rs75084363
• NM_134261.3:c.167-174986T>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.167-174986T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 152,312 control chromosomes in the GnomAD database, including 528 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 0.075 (528 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 3 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)

LOC124903500 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.138 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.167-174986T>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.167-174986T>C		intron	N/A	ENSP00000335087.6
	RORA	ENST00000551975.5	TSL:3	n.80-174986T>C		intron	N/A	ENSP00000449482.1
	RORA	ENST00000557822.5	TSL:4	n.192-174986T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0751 AC: 11435 AN: 152194 Hom.: 524 Cov.: 32

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0735

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0903

Gnomad OTH AF: 0.0888

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

GnomAD4 genome AF: 0.0751 AC: 11434 AN: 152312 Hom.: 528 Cov.: 32 AF XY: 0.0771 AC XY: 5744 AN XY: 74468

African (AFR) AF: 0.0188 AC: 782 AN: 41570

American (AMR) AF: 0.0732 AC: 1120 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 571 AN: 3472

East Asian (EAS) AF: 0.147 AC: 761 AN: 5182

South Asian (SAS) AF: 0.110 AC: 532 AN: 4826

European-Finnish (FIN) AF: 0.116 AC: 1228 AN: 10606

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0903 AC: 6145 AN: 68028

Other (OTH) AF: 0.0870 AC: 184 AN: 2116

Alfa AF: 0.0851 Hom.: 219

Bravo AF: 0.0721

Asia WGS AF: 0.107 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.63
PhyloP100		0.12
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: rs75084363; hg19: chr15-61145871;