chr15-60787178-G-A

Variant names:

• chr15-60787178-G-A
• rs12915776
• NM_134261.3:c.167-108492C>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.167-108492C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,098 control chromosomes in the GnomAD database, including 3,119 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 0.20 (3119 hom., cov: 33)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• Publications: 12 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.262 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.167-108492C>T		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.167-108492C>T		intron	N/A	ENSP00000335087.6
	RORA	ENST00000551975.5	TSL:3	n.80-108492C>T		intron	N/A	ENSP00000449482.1
	RORA	ENST00000557822.5	TSL:4	n.192-108492C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30584 AN: 151980 Hom.: 3113 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.201 AC: 30612 AN: 152098 Hom.: 3119 Cov.: 33 AF XY: 0.201 AC XY: 14935 AN XY: 74342

African (AFR) AF: 0.223 AC: 9246 AN: 41484

American (AMR) AF: 0.183 AC: 2804 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 587 AN: 3472

East Asian (EAS) AF: 0.202 AC: 1044 AN: 5174

South Asian (SAS) AF: 0.274 AC: 1322 AN: 4818

European-Finnish (FIN) AF: 0.190 AC: 2008 AN: 10574

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12986 AN: 67970

Other (OTH) AF: 0.198 AC: 419 AN: 2114

Alfa AF: 0.194 Hom.: 11296

Bravo AF: 0.199

Asia WGS AF: 0.247 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.44
PhyloP100		-0.050
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: rs12915776; hg19: chr15-61079377;