15-60502450-C-T

Variant names:

• chr15-60502450-C-T
• rs12594972
• NM_134261.3:c.1183+310G>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.1183+310G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 152,114 control chromosomes in the GnomAD database, including 52,858 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 0.82 (52858 hom., cov: 31)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.544
• Publications: 8 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.1183+310G>A		intron_variant	Intron 8 of 10	ENST00000335670.11	NP_599023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.1183+310G>A		intron_variant	Intron 8 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.823 AC: 125078 AN: 151996 Hom.: 52821 Cov.: 31

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.921

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.832

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

GnomAD4 genome AF: 0.823 AC: 125166 AN: 152114 Hom.: 52858 Cov.: 31 AF XY: 0.827 AC XY: 61511 AN XY: 74378

African (AFR) AF: 0.612 AC: 25346 AN: 41428

American (AMR) AF: 0.864 AC: 13208 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3041 AN: 3472

East Asian (EAS) AF: 0.950 AC: 4928 AN: 5188

South Asian (SAS) AF: 0.938 AC: 4522 AN: 4820

European-Finnish (FIN) AF: 0.921 AC: 9769 AN: 10602

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61555 AN: 68002

Other (OTH) AF: 0.834 AC: 1759 AN: 2110

Alfa AF: 0.879 Hom.: 99005

Bravo AF: 0.810

Asia WGS AF: 0.925 AC: 3216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.8
DANN	Benign	0.57
PhyloP100		0.54
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: rs12594972; hg19: chr15-60794649;