rs340005

chr15-60585831-G-Achr15-60585831-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.81).
• 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/exons	MANE	UniProt
RORA	NM_134261.3	c.197-53980C>T		intron_variant		ENST00000335670.11
RORA-AS1	NR_120342.1	n.416-12617G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORA	ENST00000335670.11	c.197-53980C>T		intron_variant		1	NM_134261.3
RORA-AS1	ENST00000559824.5	n.416-12617G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.759

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.651

Alfa AF: 0.621 Hom.: 50250

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

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: rs340005; hg19: chr15-60878030;