rs12914272

Variant names:

• chr15-60770768-A-G
• rs12914272
• NM_134261.3:c.167-92082T>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.167-92082T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,946 control chromosomes in the GnomAD database, including 26,381 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 0.58 (26381 hom., cov: 31)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 9 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.167-92082T>C		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1751-92082T>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.167-92082T>C		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88426 AN: 151828 Hom.: 26366 Cov.: 31

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.582 AC: 88482 AN: 151946 Hom.: 26381 Cov.: 31 AF XY: 0.582 AC XY: 43229 AN XY: 74240

African (AFR) AF: 0.466 AC: 19288 AN: 41426

American (AMR) AF: 0.607 AC: 9270 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2100 AN: 3470

East Asian (EAS) AF: 0.371 AC: 1914 AN: 5162

South Asian (SAS) AF: 0.693 AC: 3334 AN: 4812

European-Finnish (FIN) AF: 0.646 AC: 6805 AN: 10540

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.644 AC: 43786 AN: 67956

Other (OTH) AF: 0.556 AC: 1174 AN: 2110

Alfa AF: 0.618 Hom.: 3805

Bravo AF: 0.568

Asia WGS AF: 0.544 AC: 1885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	0.28
PhyloP100		-1.1
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: rs12914272; hg19: chr15-61062967;