rs339969

Variant names:

• chr15-60591082-C-A
• rs339969
• NM_134261.3:c.197-59231G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-60591082-C-A
• chr15-60591082-C-G

Variant summary

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

The NM_134261.3(RORA):​c.197-59231G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 152,064 control chromosomes in the GnomAD database, including 35,309 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 0.68 (35309 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97
• Publications: 30 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=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 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.197-59231G>T		intron	N/A	NP_599023.1	P35398-2
	RORA	NM_134260.3		c.138-32776G>T		intron	N/A	NP_599022.1	P35398-1
	RORA	NM_002943.4		c.271+23812G>T		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.197-59231G>T		intron	N/A	ENSP00000335087.6	P35398-2
	RORA	ENST00000261523.9	TSL:1	c.138-32776G>T		intron	N/A	ENSP00000261523.5	P35398-1
	RORA	ENST00000309157.8	TSL:1	c.271+23812G>T		intron	N/A	ENSP00000309753.3	A0A0C4DFP5

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102621 AN: 151946 Hom.: 35271 Cov.: 32

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.676 AC: 102724 AN: 152064 Hom.: 35309 Cov.: 32 AF XY: 0.681 AC XY: 50592 AN XY: 74314

African (AFR) AF: 0.774 AC: 32114 AN: 41474

American (AMR) AF: 0.630 AC: 9634 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2052 AN: 3470

East Asian (EAS) AF: 0.898 AC: 4633 AN: 5162

South Asian (SAS) AF: 0.605 AC: 2916 AN: 4820

European-Finnish (FIN) AF: 0.722 AC: 7639 AN: 10574

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41622 AN: 67962

Other (OTH) AF: 0.648 AC: 1368 AN: 2112

Alfa AF: 0.628 Hom.: 139110

Bravo AF: 0.673

Asia WGS AF: 0.741 AC: 2575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.93
PhyloP100		2.0
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: rs339969; hg19: chr15-60883281;