rs1403737

Variant names:

• chr15-61024003-G-A
• rs1403737
• NM_134261.3:c.166+205050C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000335670.11(RORA):​c.166+205050C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,836 control chromosomes in the GnomAD database, including 10,766 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 0.36 (10766 hom., cov: 31)
• Consequence: RORA ENST00000335670.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000335670.11. 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.166+205050C>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.166+205050C>T		intron	N/A	ENSP00000335087.6
	RORA	ENST00000551975.5	TSL:3	n.79+205050C>T		intron	N/A	ENSP00000449482.1
	RORA	ENST00000557822.5	TSL:4	n.191+205050C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55050 AN: 151716 Hom.: 10740 Cov.: 31

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.363 AC: 55122 AN: 151836 Hom.: 10766 Cov.: 31 AF XY: 0.366 AC XY: 27131 AN XY: 74194

African (AFR) AF: 0.510 AC: 21119 AN: 41400

American (AMR) AF: 0.334 AC: 5100 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1002 AN: 3472

East Asian (EAS) AF: 0.475 AC: 2440 AN: 5136

South Asian (SAS) AF: 0.363 AC: 1746 AN: 4808

European-Finnish (FIN) AF: 0.360 AC: 3791 AN: 10534

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18920 AN: 67928

Other (OTH) AF: 0.349 AC: 734 AN: 2104

Alfa AF: 0.306 Hom.: 4731

Bravo AF: 0.367

Asia WGS AF: 0.414 AC: 1441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.24
DANN	Benign	0.56
PhyloP100		-0.64
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: rs1403737; hg19: chr15-61316202; COSMIC: COSV59539845;