rs17303244

Variant names:

• chr15-60908101-T-C
• rs17303244
• NM_134261.3:c.167-229415A>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.167-229415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,172 control chromosomes in the GnomAD database, including 1,904 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 0.13 (1904 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.167-229415A>G		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1751-229415A>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.167-229415A>G		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19143 AN: 152054 Hom.: 1903 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0677

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.126 AC: 19153 AN: 152172 Hom.: 1904 Cov.: 32 AF XY: 0.136 AC XY: 10109 AN XY: 74406

African (AFR) AF: 0.129 AC: 5371 AN: 41516

American (AMR) AF: 0.189 AC: 2886 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3470

East Asian (EAS) AF: 0.534 AC: 2753 AN: 5154

South Asian (SAS) AF: 0.262 AC: 1264 AN: 4816

European-Finnish (FIN) AF: 0.138 AC: 1467 AN: 10602

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0677 AC: 4601 AN: 68008

Other (OTH) AF: 0.124 AC: 263 AN: 2114

Alfa AF: 0.0963 Hom.: 2045

Bravo AF: 0.132

Asia WGS AF: 0.363 AC: 1258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0050
DANN	Benign	0.33
PhyloP100		-2.3
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: rs17303244; hg19: chr15-61200300;