rs1568717

Variant names:

• chr15-61070248-C-A
• rs1568717
• NM_134261.3:c.166+158805G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-61070248-C-A
• chr15-61070248-C-G

Variant summary

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

The NM_134261.3(RORA):​c.166+158805G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,998 control chromosomes in the GnomAD database, including 4,684 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 0.24 (4684 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• Publications: 5 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)

LOC107984805 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.166+158805G>T		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.166+158805G>T		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36963 AN: 151880 Hom.: 4679 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.243 AC: 36989 AN: 151998 Hom.: 4684 Cov.: 32 AF XY: 0.237 AC XY: 17585 AN XY: 74294

African (AFR) AF: 0.255 AC: 10564 AN: 41442

American (AMR) AF: 0.217 AC: 3312 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 796 AN: 3472

East Asian (EAS) AF: 0.00271 AC: 14 AN: 5172

South Asian (SAS) AF: 0.153 AC: 736 AN: 4810

European-Finnish (FIN) AF: 0.228 AC: 2410 AN: 10554

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18437 AN: 67960

Other (OTH) AF: 0.228 AC: 480 AN: 2106

Alfa AF: 0.261 Hom.: 14501

Bravo AF: 0.245

Asia WGS AF: 0.0950 AC: 333 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	2.3
DANN	Benign	0.46
PhyloP100		-0.23
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: rs1568717; hg19: chr15-61362447;