rs782908

Variant names:

• chr15-61086411-G-A
• rs782908
• NM_134261.3:c.166+142642C>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.166+142642C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,170 control chromosomes in the GnomAD database, including 2,094 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 0.16 (2094 hom., cov: 33)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 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.166+142642C>T		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.166+142642C>T		intron	N/A	ENSP00000335087.6
	RORA	ENST00000551975.5	TSL:3	n.79+142642C>T		intron	N/A	ENSP00000449482.1
	RORA	ENST00000557822.5	TSL:4	n.191+142642C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24458 AN: 152052 Hom.: 2085 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.161 AC: 24475 AN: 152170 Hom.: 2094 Cov.: 33 AF XY: 0.161 AC XY: 11963 AN XY: 74412

African (AFR) AF: 0.196 AC: 8124 AN: 41500

American (AMR) AF: 0.101 AC: 1549 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3466

East Asian (EAS) AF: 0.169 AC: 873 AN: 5178

South Asian (SAS) AF: 0.193 AC: 930 AN: 4824

European-Finnish (FIN) AF: 0.176 AC: 1864 AN: 10580

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10158 AN: 68008

Other (OTH) AF: 0.141 AC: 297 AN: 2112

Alfa AF: 0.150 Hom.: 627

Bravo AF: 0.155

Asia WGS AF: 0.172 AC: 596 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	0.67
PhyloP100		-0.13
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: rs782908; hg19: chr15-61378610;