rs11632352

Positions:

• chr15-61065667-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134261.3(RORA):​c.166+163386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,050 control chromosomes in the GnomAD database, including 9,329 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 0.35 (9329 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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]

LOC107984805 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORA	NM_134261.3	c.166+163386G>A		intron_variant		ENST00000335670.11	NP_599023.1
LOC107984805	XR_007064660.1	n.41223-24533G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.166+163386G>A		intron_variant		1	NM_134261.3	ENSP00000335087

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52584 AN: 151932 Hom.: 9315 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.346 AC: 52621 AN: 152050 Hom.: 9329 Cov.: 32 AF XY: 0.349 AC XY: 25933 AN XY: 74326

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.330

Alfa AF: 0.358 Hom.: 1881

Bravo AF: 0.340

Asia WGS AF: 0.270 AC: 937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.8
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs11632352; hg19: chr15-61357866;