rs1863270

Variant names:

• chr15-60720060-C-A
• rs1863270
• NM_134261.3:c.167-41374G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-60720060-C-A
• chr15-60720060-C-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.167-41374G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,070 control chromosomes in the GnomAD database, including 42,451 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 0.74 (42451 hom., cov: 31)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 11 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.167-41374G>T		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1751-41374G>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.167-41374G>T		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113041 AN: 151952 Hom.: 42428 Cov.: 31

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.744 AC: 113114 AN: 152070 Hom.: 42451 Cov.: 31 AF XY: 0.745 AC XY: 55393 AN XY: 74316

African (AFR) AF: 0.822 AC: 34130 AN: 41502

American (AMR) AF: 0.689 AC: 10520 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2382 AN: 3470

East Asian (EAS) AF: 0.940 AC: 4870 AN: 5182

South Asian (SAS) AF: 0.726 AC: 3492 AN: 4812

European-Finnish (FIN) AF: 0.740 AC: 7808 AN: 10554

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47517 AN: 67970

Other (OTH) AF: 0.702 AC: 1486 AN: 2116

Alfa AF: 0.711 Hom.: 176399

Bravo AF: 0.743

Asia WGS AF: 0.830 AC: 2885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.54
PhyloP100		-0.067
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: rs1863270; hg19: chr15-61012259;