rs16943429

Variant names:

• chr15-60987054-T-C
• rs16943429
• NM_134261.3:c.166+241999A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-60987054-T-C
• chr15-60987054-T-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+241999A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,164 control chromosomes in the GnomAD database, including 3,903 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 0.22 (3903 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.766
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.166+241999A>G		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1752+241999A>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.166+241999A>G		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33383 AN: 152046 Hom.: 3892 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.220 AC: 33416 AN: 152164 Hom.: 3903 Cov.: 32 AF XY: 0.222 AC XY: 16545 AN XY: 74390

African (AFR) AF: 0.278 AC: 11525 AN: 41498

American (AMR) AF: 0.225 AC: 3437 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 777 AN: 3472

East Asian (EAS) AF: 0.175 AC: 907 AN: 5180

South Asian (SAS) AF: 0.179 AC: 861 AN: 4820

European-Finnish (FIN) AF: 0.221 AC: 2341 AN: 10574

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12944 AN: 68012

Other (OTH) AF: 0.224 AC: 473 AN: 2112

Alfa AF: 0.220 Hom.: 630

Bravo AF: 0.221

Asia WGS AF: 0.190 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.7
DANN	Benign	0.73
PhyloP100		0.77
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: rs16943429; hg19: chr15-61279253;