15-61093881-C-T

Variant names:

• chr15-61093881-C-T
• rs1437539
• NM_134261.3:c.166+135172G>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.166+135172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,052 control chromosomes in the GnomAD database, including 10,569 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 0.37 (10569 hom., cov: 33)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.166+135172G>A		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.166+135172G>A		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55712 AN: 151934 Hom.: 10546 Cov.: 33

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.367 AC: 55778 AN: 152052 Hom.: 10569 Cov.: 33 AF XY: 0.363 AC XY: 26946 AN XY: 74330

African (AFR) AF: 0.434 AC: 18002 AN: 41482

American (AMR) AF: 0.381 AC: 5828 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1073 AN: 3472

East Asian (EAS) AF: 0.144 AC: 744 AN: 5152

South Asian (SAS) AF: 0.284 AC: 1364 AN: 4810

European-Finnish (FIN) AF: 0.360 AC: 3800 AN: 10552

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23893 AN: 67982

Other (OTH) AF: 0.345 AC: 727 AN: 2110

Alfa AF: 0.296 Hom.: 1128

Bravo AF: 0.375

Asia WGS AF: 0.262 AC: 917 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.4
DANN	Benign	0.52
PhyloP100		-0.15
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: rs1437539; hg19: chr15-61386080;