rs11632600

Variant names:

• chr15-60581471-G-T
• rs11632600
• NM_134261.3:c.197-49620C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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-AS1 (HGNC:51410): (RORA antisense RNA 1)

ENSG00000309525 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.197-49620C>A		intron_variant	Intron 2 of 10	ENST00000335670.11	NP_599023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.197-49620C>A		intron_variant	Intron 2 of 10	1	NM_134261.3	ENSP00000335087.6

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

African (AFR) AF: 0.0524 AC: 2177 AN: 41534

American (AMR) AF: 0.140 AC: 2134 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3472

East Asian (EAS) AF: 0.179 AC: 930 AN: 5186

South Asian (SAS) AF: 0.133 AC: 640 AN: 4818

European-Finnish (FIN) AF: 0.143 AC: 1516 AN: 10578

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10902 AN: 67974

Other (OTH) AF: 0.148 AC: 313 AN: 2114

Alfa AF: 0.145 Hom.: 4621

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
PhyloP100		-0.46
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: rs11632600; hg19: chr15-60873670;