NM_134261.3:c.197-53980C>T

Variant names:

• chr15-60585831-G-A
• rs340005
• NM_134261.3:c.197-53980C>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.197-53980C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 151,976 control chromosomes in the GnomAD database, including 35,056 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 0.67 (35056 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• Publications: 27 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.197-53980C>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.197-53980C>T		intron_variant	Intron 2 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102365 AN: 151858 Hom.: 35030 Cov.: 32

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.674 AC: 102451 AN: 151976 Hom.: 35056 Cov.: 32 AF XY: 0.679 AC XY: 50442 AN XY: 74260

African (AFR) AF: 0.759 AC: 31448 AN: 41432

American (AMR) AF: 0.636 AC: 9709 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2058 AN: 3470

East Asian (EAS) AF: 0.898 AC: 4649 AN: 5178

South Asian (SAS) AF: 0.607 AC: 2921 AN: 4814

European-Finnish (FIN) AF: 0.727 AC: 7670 AN: 10554

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41877 AN: 67954

Other (OTH) AF: 0.651 AC: 1370 AN: 2104

Alfa AF: 0.633 Hom.: 90305

Bravo AF: 0.671

Asia WGS AF: 0.735 AC: 2554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.71
PhyloP100		-0.019
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: rs340005; hg19: chr15-60878030;