15-60863129-C-T

Variant names:

• chr15-60863129-C-T
• rs8041466
• NM_134261.3:c.167-184443G>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.167-184443G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,008 control chromosomes in the GnomAD database, including 9,215 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 0.34 (9215 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.854
• Publications: 8 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)

LOC102724802 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.167-184443G>A		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1
LOC102724802	XR_001751785.2	n.7140C>T		non_coding_transcript_exon_variant	Exon 1 of 5
RORA	XM_047432928.1	c.-1751-184443G>A		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.167-184443G>A		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52215 AN: 151890 Hom.: 9192 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.344 AC: 52279 AN: 152008 Hom.: 9215 Cov.: 32 AF XY: 0.343 AC XY: 25513 AN XY: 74320

African (AFR) AF: 0.326 AC: 13519 AN: 41434

American (AMR) AF: 0.274 AC: 4190 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1196 AN: 3468

East Asian (EAS) AF: 0.238 AC: 1231 AN: 5178

South Asian (SAS) AF: 0.373 AC: 1798 AN: 4822

European-Finnish (FIN) AF: 0.392 AC: 4136 AN: 10554

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25052 AN: 67954

Other (OTH) AF: 0.278 AC: 585 AN: 2108

Alfa AF: 0.349 Hom.: 26623

Bravo AF: 0.328

Asia WGS AF: 0.309 AC: 1074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.39
PhyloP100		-0.85
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: rs8041466; hg19: chr15-61155328;