NM_134261.3:c.167-135575G>A

Variant names:

• chr15-60814261-C-T
• rs79610262
• NM_134261.3:c.167-135575G>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.167-135575G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0697 in 152,180 control chromosomes in the GnomAD database, including 532 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 0.070 (532 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.615
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.121 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.167-135575G>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.167-135575G>A		intron	N/A	ENSP00000335087.6
	RORA	ENST00000551975.5	TSL:3	n.80-135575G>A		intron	N/A	ENSP00000449482.1
	RORA	ENST00000557822.5	TSL:4	n.192-135575G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0697 AC: 10596 AN: 152062 Hom.: 527 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0674

Gnomad FIN AF: 0.0893

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0348

Gnomad OTH AF: 0.0540

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

GnomAD4 genome AF: 0.0697 AC: 10604 AN: 152180 Hom.: 532 Cov.: 32 AF XY: 0.0722 AC XY: 5374 AN XY: 74402

African (AFR) AF: 0.102 AC: 4244 AN: 41514

American (AMR) AF: 0.126 AC: 1919 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3472

East Asian (EAS) AF: 0.114 AC: 591 AN: 5166

South Asian (SAS) AF: 0.0672 AC: 324 AN: 4820

European-Finnish (FIN) AF: 0.0893 AC: 947 AN: 10606

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0348 AC: 2370 AN: 68030

Other (OTH) AF: 0.0530 AC: 112 AN: 2114

Alfa AF: 0.0588 Hom.: 119

Bravo AF: 0.0765

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.38
DANN	Benign	0.72
PhyloP100		-0.61
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: rs79610262; hg19: chr15-61106460;