15-60855305-T-C

Variant names:

• chr15-60855305-T-C
• rs11632098
• NM_134261.3:c.167-176619A>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.167-176619A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,134 control chromosomes in the GnomAD database, including 58,702 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 0.87 (58702 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.840
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.167-176619A>G		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1751-176619A>G		intron_variant	Intron 1 of 10		XP_047288884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.167-176619A>G		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132748 AN: 152016 Hom.: 58658 Cov.: 32

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.916

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.870

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

GnomAD4 genome AF: 0.873 AC: 132847 AN: 152134 Hom.: 58702 Cov.: 32 AF XY: 0.877 AC XY: 65238 AN XY: 74380

African (AFR) AF: 0.727 AC: 30139 AN: 41430

American (AMR) AF: 0.916 AC: 14021 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 3211 AN: 3470

East Asian (EAS) AF: 0.992 AC: 5146 AN: 5186

South Asian (SAS) AF: 0.951 AC: 4578 AN: 4814

European-Finnish (FIN) AF: 0.940 AC: 9973 AN: 10604

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.924 AC: 62838 AN: 68010

Other (OTH) AF: 0.872 AC: 1843 AN: 2114

Alfa AF: 0.890 Hom.: 7851

Bravo AF: 0.865

Asia WGS AF: 0.962 AC: 3347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		0.84
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: rs11632098; hg19: chr15-61147504;