rs1403737

chr15-61024003-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134261.3(RORA):c.166+205050C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,836 control chromosomes in the GnomAD database, including 10,766 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 0.36 (10766 hom., cov: 31)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640

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]

LOC107984805 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RORA	NM_134261.3	c.166+205050C>T		intron_variant		ENST00000335670.11
LOC107984805	XR_007064660.1	n.47519-7968C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORA	ENST00000335670.11	c.166+205050C>T		intron_variant		1	NM_134261.3

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55050 AN: 151716 Hom.: 10740 Cov.: 31

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.363 AC: 55122 AN: 151836 Hom.: 10766 Cov.: 31 AF XY: 0.366 AC XY: 27131 AN XY: 74194

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.349

Alfa AF: 0.307 Hom.: 4327

Bravo AF: 0.367

Asia WGS AF: 0.414 AC: 1441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.24
Dann	Benign	0.56

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: rs1403737; hg19: chr15-61316202; COSMIC: COSV59539845;