chr15-60932100-A-C

Position:

• chr15-60932100-A-C

Variant summary

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

The NM_134261.3(RORA):​c.167-253414T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 152,246 control chromosomes in the GnomAD database, including 179 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 0.039 (179 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.712

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 (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 = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORA	NM_134261.3	c.167-253414T>G		intron_variant		ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1751-253414T>G		intron_variant			XP_047288884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.167-253414T>G		intron_variant		1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5929 AN: 152128 Hom.: 174 Cov.: 32

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0297

Gnomad ASJ AF: 0.00750

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0204

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0574

Gnomad OTH AF: 0.0372

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

GnomAD4 genome AF: 0.0390 AC: 5942 AN: 152246 Hom.: 179 Cov.: 32 AF XY: 0.0376 AC XY: 2801 AN XY: 74448

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.0296

Gnomad4 ASJ AF: 0.00750

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0352

Gnomad4 FIN AF: 0.0204

Gnomad4 NFE AF: 0.0574

Gnomad4 OTH AF: 0.0449

Alfa AF: 0.0478 Hom.: 37

Bravo AF: 0.0388

Asia WGS AF: 0.0770 AC: 267 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	4.6
DANN	Benign	0.54

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: rs79995443; hg19: chr15-61224299;