15-61144791-T-C

Variant names:

• chr15-61144791-T-C
• rs11854222
• NM_134261.3:c.166+84262A>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+84262A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 152,006 control chromosomes in the GnomAD database, including 36,417 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 0.68 (36417 hom., cov: 31)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• 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: 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.769 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.166+84262A>G		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+84262A>G		intron	N/A	ENSP00000335087.6
	RORA	ENST00000551975.5	TSL:3	n.79+84262A>G		intron	N/A	ENSP00000449482.1
	RORA	ENST00000557822.5	TSL:4	n.191+84262A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103635 AN: 151888 Hom.: 36392 Cov.: 31

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.653

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

GnomAD4 genome AF: 0.682 AC: 103700 AN: 152006 Hom.: 36417 Cov.: 31 AF XY: 0.674 AC XY: 50102 AN XY: 74300

African (AFR) AF: 0.605 AC: 25081 AN: 41444

American (AMR) AF: 0.529 AC: 8079 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2451 AN: 3468

East Asian (EAS) AF: 0.446 AC: 2299 AN: 5156

South Asian (SAS) AF: 0.532 AC: 2562 AN: 4814

European-Finnish (FIN) AF: 0.780 AC: 8231 AN: 10552

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.774 AC: 52617 AN: 67968

Other (OTH) AF: 0.655 AC: 1385 AN: 2114

Alfa AF: 0.722 Hom.: 58436

Bravo AF: 0.661

Asia WGS AF: 0.478 AC: 1662 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.8
DANN	Benign	0.83
PhyloP100		-0.039
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: rs11854222; hg19: chr15-61436990;