rs1482057

Variant names:

• chr15-60772552-A-C
• rs1482057
• NM_134261.3:c.167-93866T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-60772552-A-C
• chr15-60772552-A-G
• chr15-60772552-A-T

Variant summary

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

The NM_134261.3(RORA):​c.167-93866T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,150 control chromosomes in the GnomAD database, including 48,894 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 0.80 (48894 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 19 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.167-93866T>G		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1751-93866T>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.167-93866T>G		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121785 AN: 152032 Hom.: 48853 Cov.: 32

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.811

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.786

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

GnomAD4 genome AF: 0.801 AC: 121878 AN: 152150 Hom.: 48894 Cov.: 32 AF XY: 0.803 AC XY: 59744 AN XY: 74382

African (AFR) AF: 0.774 AC: 32111 AN: 41490

American (AMR) AF: 0.818 AC: 12506 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.811 AC: 2816 AN: 3472

East Asian (EAS) AF: 0.848 AC: 4394 AN: 5180

South Asian (SAS) AF: 0.895 AC: 4326 AN: 4832

European-Finnish (FIN) AF: 0.834 AC: 8826 AN: 10586

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54253 AN: 67986

Other (OTH) AF: 0.781 AC: 1647 AN: 2110

Alfa AF: 0.805 Hom.: 13610

Bravo AF: 0.797

Asia WGS AF: 0.860 AC: 2984 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.18
DANN	Benign	0.33
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1482057; hg19: chr15-61064751;