rs726914

Variant names:

• chr15-61203259-G-A
• rs726914
• NM_134261.3:c.166+25794C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-61203259-G-A
• chr15-61203259-G-C

Variant summary

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

The NM_134261.3(RORA):​c.166+25794C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,084 control chromosomes in the GnomAD database, including 6,600 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 0.27 (6600 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441

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]

LOC105370841 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.166+25794C>T		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1752+25794C>T		intron_variant	Intron 1 of 10		XP_047288884.1
LOC105370841	XR_001751772.2	n.17735C>T		non_coding_transcript_exon_variant	Exon 3 of 3
LOC105370841	XR_007064661.1	n.17971C>T		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.166+25794C>T		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40928 AN: 151964 Hom.: 6598 Cov.: 32

Gnomad AFR AF: 0.0931

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.269 AC: 40925 AN: 152084 Hom.: 6600 Cov.: 32 AF XY: 0.269 AC XY: 19965 AN XY: 74326

Gnomad4 AFR AF: 0.0928

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.283

Alfa AF: 0.337 Hom.: 18157

Bravo AF: 0.258

Asia WGS AF: 0.322 AC: 1117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.34

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: rs726914; hg19: chr15-61495458; COSMIC: COSV59530599;