rs235512

Variant names:

• chr15-60623271-G-A
• rs235512
• NM_134261.3:c.196+55386C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134261.3(RORA):​c.196+55386C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 151,992 control chromosomes in the GnomAD database, including 26,433 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 0.59 (26433 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.196+55386C>T		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.196+55386C>T		intron_variant	Intron 2 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89558 AN: 151874 Hom.: 26397 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.590 AC: 89652 AN: 151992 Hom.: 26433 Cov.: 32 AF XY: 0.594 AC XY: 44162 AN XY: 74304

African (AFR) AF: 0.604 AC: 25030 AN: 41474

American (AMR) AF: 0.590 AC: 9017 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1793 AN: 3466

East Asian (EAS) AF: 0.680 AC: 3515 AN: 5168

South Asian (SAS) AF: 0.582 AC: 2797 AN: 4804

European-Finnish (FIN) AF: 0.650 AC: 6872 AN: 10568

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38559 AN: 67912

Other (OTH) AF: 0.581 AC: 1228 AN: 2114

Alfa AF: 0.579 Hom.: 3644

Bravo AF: 0.584

Asia WGS AF: 0.638 AC: 2216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.32
DANN	Benign	0.18
PhyloP100		0.19
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: rs235512; hg19: chr15-60915470;