rs12909890

Positions:

• chr15-60725778-G-A
• chr15-60725778-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RORA	NM_134261.3	c.167-47092C>T		intron_variant		ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1751-47092C>T		intron_variant			XP_047288884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.167-47092C>T		intron_variant		1	NM_134261.3	ENSP00000335087

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

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.514

Alfa AF: 0.578 Hom.: 14855

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12909890; hg19: chr15-61017977;