rs12909890

Variant names:

• chr15-60725778-G-A
• rs12909890
• NM_134261.3:c.167-47092C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-60725778-G-A
• chr15-60725778-G-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.167-47092C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,934 control chromosomes in the GnomAD database, including 21,951 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 0.49 (21951 hom., cov: 31)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• 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)

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 (AMR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.167-47092C>T		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1751-47092C>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.167-47092C>T		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73995 AN: 151814 Hom.: 21947 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.487 AC: 73989 AN: 151934 Hom.: 21951 Cov.: 31 AF XY: 0.491 AC XY: 36451 AN XY: 74264

African (AFR) AF: 0.122 AC: 5051 AN: 41432

American (AMR) AF: 0.649 AC: 9911 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2181 AN: 3468

East Asian (EAS) AF: 0.482 AC: 2480 AN: 5142

South Asian (SAS) AF: 0.593 AC: 2850 AN: 4810

European-Finnish (FIN) AF: 0.628 AC: 6629 AN: 10560

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43039 AN: 67934

Other (OTH) AF: 0.514 AC: 1084 AN: 2108

Alfa AF: 0.577 Hom.: 24422

Bravo AF: 0.474

Asia WGS AF: 0.495 AC: 1718 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	2.5
DANN	Benign	0.67
PhyloP100		0.13
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: rs12909890; hg19: chr15-61017977;