NM_134261.3:c.167-102917G>C

Variant names:

• chr15-60781603-C-G
• rs17270446
• NM_134261.3:c.167-102917G>C

Variant summary

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

The NM_134261.3(RORA):​c.167-102917G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,172 control chromosomes in the GnomAD database, including 7,233 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 0.28 (7233 hom., cov: 29)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• 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=-0.63).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.167-102917G>C		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1751-102917G>C		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.167-102917G>C		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42786 AN: 151054 Hom.: 7234 Cov.: 29

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.283 AC: 42782 AN: 151172 Hom.: 7233 Cov.: 29 AF XY: 0.282 AC XY: 20814 AN XY: 73740

African (AFR) AF: 0.101 AC: 4149 AN: 41184

American (AMR) AF: 0.415 AC: 6311 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1119 AN: 3464

East Asian (EAS) AF: 0.180 AC: 912 AN: 5068

South Asian (SAS) AF: 0.280 AC: 1329 AN: 4750

European-Finnish (FIN) AF: 0.300 AC: 3106 AN: 10364

Middle Eastern (MID) AF: 0.285 AC: 82 AN: 288

European-Non Finnish (NFE) AF: 0.366 AC: 24863 AN: 67864

Other (OTH) AF: 0.295 AC: 617 AN: 2090

Alfa AF: 0.211 Hom.: 515

Bravo AF: 0.285

Asia WGS AF: 0.243 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.46
PhyloP100		1.6
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: rs17270446; hg19: chr15-61073802;