chr15-60820523-G-A

Variant names:

• chr15-60820523-G-A
• rs10519077
• NM_134261.3:c.167-141837C>T

Variant summary

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

The NM_134261.3(RORA):​c.167-141837C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 151,926 control chromosomes in the GnomAD database, including 36,330 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 0.69 (36330 hom., cov: 31)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.167-141837C>T		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1751-141837C>T		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.167-141837C>T		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104770 AN: 151808 Hom.: 36296 Cov.: 31

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.702

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

GnomAD4 genome AF: 0.690 AC: 104853 AN: 151926 Hom.: 36330 Cov.: 31 AF XY: 0.691 AC XY: 51316 AN XY: 74236

African (AFR) AF: 0.676 AC: 27996 AN: 41404

American (AMR) AF: 0.626 AC: 9556 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2516 AN: 3468

East Asian (EAS) AF: 0.835 AC: 4314 AN: 5164

South Asian (SAS) AF: 0.816 AC: 3919 AN: 4804

European-Finnish (FIN) AF: 0.673 AC: 7090 AN: 10542

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47087 AN: 67972

Other (OTH) AF: 0.705 AC: 1487 AN: 2110

Alfa AF: 0.684 Hom.: 15988

Bravo AF: 0.682

Asia WGS AF: 0.795 AC: 2764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.75
PhyloP100		0.38
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: rs10519077; hg19: chr15-61112722;