rs8041381

Variant names:

• chr15-60570763-A-G
• rs8041381
• NM_134261.3:c.197-38912T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134261.3(RORA):​c.197-38912T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,034 control chromosomes in the GnomAD database, including 14,647 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 0.41 (14647 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644
• Publications: 18 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.197-38912T>C		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.197-38912T>C		intron_variant	Intron 2 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61753 AN: 151916 Hom.: 14620 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.0994

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.407 AC: 61836 AN: 152034 Hom.: 14647 Cov.: 32 AF XY: 0.398 AC XY: 29551 AN XY: 74302

African (AFR) AF: 0.658 AC: 27251 AN: 41442

American (AMR) AF: 0.320 AC: 4884 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1400 AN: 3470

East Asian (EAS) AF: 0.101 AC: 522 AN: 5178

South Asian (SAS) AF: 0.168 AC: 811 AN: 4818

European-Finnish (FIN) AF: 0.290 AC: 3063 AN: 10558

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22713 AN: 67972

Other (OTH) AF: 0.398 AC: 839 AN: 2106

Alfa AF: 0.358 Hom.: 23073

Bravo AF: 0.426

Asia WGS AF: 0.187 AC: 653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.59
PhyloP100		-0.64
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: rs8041381; hg19: chr15-60862962;