chr15-60602766-C-T

Variant names:

• chr15-60602766-C-T
• rs340029
• NM_134261.3:c.197-70915G>A

Variant summary

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

The NM_134261.3(RORA):​c.197-70915G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 152,090 control chromosomes in the GnomAD database, including 37,580 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 0.69 (37580 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239
• Publications: 31 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134261.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	NM_134261.3	MANE Select	c.197-70915G>A		intron	N/A	NP_599023.1	P35398-2
	RORA	NM_134260.3		c.137+24472G>A		intron	N/A	NP_599022.1	P35398-1
	RORA	NM_002943.4		c.271+12128G>A		intron	N/A	NP_002934.1	A0A0C4DFP5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	ENST00000335670.11	TSL:1 MANE Select	c.197-70915G>A		intron	N/A	ENSP00000335087.6	P35398-2
	RORA	ENST00000261523.9	TSL:1	c.137+24472G>A		intron	N/A	ENSP00000261523.5	P35398-1
	RORA	ENST00000309157.8	TSL:1	c.271+12128G>A		intron	N/A	ENSP00000309753.3	A0A0C4DFP5

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105569 AN: 151972 Hom.: 37529 Cov.: 32

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.695 AC: 105687 AN: 152090 Hom.: 37580 Cov.: 32 AF XY: 0.699 AC XY: 51966 AN XY: 74346

African (AFR) AF: 0.829 AC: 34382 AN: 41498

American (AMR) AF: 0.644 AC: 9823 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2069 AN: 3468

East Asian (EAS) AF: 0.907 AC: 4708 AN: 5188

South Asian (SAS) AF: 0.620 AC: 2992 AN: 4822

European-Finnish (FIN) AF: 0.723 AC: 7649 AN: 10578

Middle Eastern (MID) AF: 0.575 AC: 168 AN: 292

European-Non Finnish (NFE) AF: 0.617 AC: 41908 AN: 67962

Other (OTH) AF: 0.667 AC: 1409 AN: 2112

Alfa AF: 0.647 Hom.: 57330

Bravo AF: 0.695

Asia WGS AF: 0.760 AC: 2640 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.84
DANN	Benign	0.51
PhyloP100		-0.24
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: rs340029; hg19: chr15-60894965;