rs11632600

Positions:

• chr15-60581471-G-T

Variant summary

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

The NM_134261.3(RORA):​c.197-49620C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,174 control chromosomes in the GnomAD database, including 1,384 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 0.13 (1384 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458

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-AS1 (HGNC:51410): (RORA antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RORA	NM_134261.3	c.197-49620C>A		intron_variant		ENST00000335670.11
RORA-AS1	NR_120342.1	n.416-16977G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORA	ENST00000335670.11	c.197-49620C>A		intron_variant		1	NM_134261.3
RORA-AS1	ENST00000559824.5	n.416-16977G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19343 AN: 152056 Hom.: 1390 Cov.: 32

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.127 AC: 19334 AN: 152174 Hom.: 1384 Cov.: 32 AF XY: 0.128 AC XY: 9521 AN XY: 74398

Gnomad4 AFR AF: 0.0524

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.148

Alfa AF: 0.153 Hom.: 3077

Bravo AF: 0.125

Asia WGS AF: 0.137 AC: 473 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.65
DANN	Benign	0.67

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: rs11632600; hg19: chr15-60873670;