15-61217261-T-C

Variant names:

• chr15-61217261-T-C
• rs7175393
• NM_134261.3:c.166+11792A>G

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+11792A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,094 control chromosomes in the GnomAD database, including 47,554 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 0.79 (47554 hom., cov: 31)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia

LOC105370841 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 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+11792A>G		intron	N/A	NP_599023.1	P35398-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	ENST00000335670.11	TSL:1 MANE Select	c.166+11792A>G		intron	N/A	ENSP00000335087.6	P35398-2
	RORA	ENST00000558904.2	TSL:2	c.103+11792A>G		intron	N/A	ENSP00000484955.1	A0A087X2G0
	RORA	ENST00000551975.5	TSL:3	n.79+11792A>G		intron	N/A	ENSP00000449482.1	H0YII6

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119680 AN: 151976 Hom.: 47520 Cov.: 31

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.835

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.809

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

GnomAD4 genome AF: 0.787 AC: 119762 AN: 152094 Hom.: 47554 Cov.: 31 AF XY: 0.790 AC XY: 58749 AN XY: 74372

African (AFR) AF: 0.685 AC: 28410 AN: 41448

American (AMR) AF: 0.858 AC: 13115 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2954 AN: 3472

East Asian (EAS) AF: 0.987 AC: 5105 AN: 5174

South Asian (SAS) AF: 0.867 AC: 4168 AN: 4808

European-Finnish (FIN) AF: 0.793 AC: 8396 AN: 10586

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54895 AN: 68004

Other (OTH) AF: 0.810 AC: 1708 AN: 2108

Alfa AF: 0.796 Hom.: 8583

Bravo AF: 0.788

Asia WGS AF: 0.922 AC: 3206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.0
DANN	Benign	0.33
PhyloP100		-1.1
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: rs7175393; hg19: chr15-61509460;