rs4775350

Positions:

• chr15-61041054-T-C
• chr15-61041054-T-G

Variant summary

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

The NM_134261.3(RORA):​c.166+187999A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0583 in 152,124 control chromosomes in the GnomAD database, including 400 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 0.058 (400 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORA	NM_134261.3	c.166+187999A>G		intron_variant		ENST00000335670.11	NP_599023.1
LOC107984805	XR_007064660.1	n.41303A>G		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.166+187999A>G		intron_variant		1	NM_134261.3	ENSP00000335087

Frequencies

GnomAD3 genomes AF: 0.0583 AC: 8855 AN: 152006 Hom.: 398 Cov.: 32

Gnomad AFR AF: 0.0786

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0825

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0578

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0252

Gnomad OTH AF: 0.0617

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0583 AC: 8865 AN: 152124 Hom.: 400 Cov.: 32 AF XY: 0.0635 AC XY: 4721 AN XY: 74362

Gnomad4 AFR AF: 0.0787

Gnomad4 AMR AF: 0.0825

Gnomad4 ASJ AF: 0.0291

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.0578

Gnomad4 NFE AF: 0.0252

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0223 Hom.: 16

Bravo AF: 0.0602

Asia WGS AF: 0.188 AC: 652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.26
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4775350; hg19: chr15-61333253;