rs2290430

Variant names:

• chr15-60499755-A-C
• rs2290430
• NM_134261.3:c.1407+137T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-60499755-A-C
• chr15-60499755-A-G
• chr15-60499755-A-T

Variant summary

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

The ENST00000335670.11(RORA):​c.1407+137T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0881 in 534,268 control chromosomes in the GnomAD database, including 2,235 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 0.095 (695 hom., cov: 32)
  • Exomes 𝑓: 0.086 (1540 hom.)
• Consequence: RORA ENST00000335670.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131
• Publications: 10 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000335670.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	NM_134261.3	MANE Select	c.1407+137T>G		intron	N/A	NP_599023.1
	RORA	NM_134260.3		c.1506+137T>G		intron	N/A	NP_599022.1
	RORA	NM_002943.4		c.1482+137T>G		intron	N/A	NP_002934.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	ENST00000335670.11	TSL:1 MANE Select	c.1407+137T>G		intron	N/A	ENSP00000335087.6
	RORA	ENST00000261523.9	TSL:1	c.1506+137T>G		intron	N/A	ENSP00000261523.5
	RORA	ENST00000309157.8	TSL:1	c.1482+137T>G		intron	N/A	ENSP00000309753.3

Frequencies

GnomAD3 genomes AF: 0.0947 AC: 14395 AN: 152046 Hom.: 696 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0489

Gnomad SAS AF: 0.0596

Gnomad FIN AF: 0.0788

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0937

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.0856 AC: 32689 AN: 382104 Hom.: 1540 AF XY: 0.0854 AC XY: 17138 AN XY: 200632

African (AFR) AF: 0.0989 AC: 964 AN: 9748

American (AMR) AF: 0.0999 AC: 1137 AN: 11378

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 1468 AN: 11894

East Asian (EAS) AF: 0.0348 AC: 936 AN: 26924

South Asian (SAS) AF: 0.0600 AC: 1691 AN: 28200

European-Finnish (FIN) AF: 0.0689 AC: 2296 AN: 33324

Middle Eastern (MID) AF: 0.105 AC: 327 AN: 3124

European-Non Finnish (NFE) AF: 0.0930 AC: 21830 AN: 234830

Other (OTH) AF: 0.0899 AC: 2040 AN: 22682

GnomAD4 genome AF: 0.0946 AC: 14397 AN: 152164 Hom.: 695 Cov.: 32 AF XY: 0.0936 AC XY: 6962 AN XY: 74398

African (AFR) AF: 0.101 AC: 4176 AN: 41504

American (AMR) AF: 0.109 AC: 1660 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 432 AN: 3468

East Asian (EAS) AF: 0.0494 AC: 256 AN: 5178

South Asian (SAS) AF: 0.0590 AC: 284 AN: 4810

European-Finnish (FIN) AF: 0.0788 AC: 834 AN: 10588

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0936 AC: 6368 AN: 68012

Other (OTH) AF: 0.106 AC: 223 AN: 2106

Alfa AF: 0.0921 Hom.: 1312

Bravo AF: 0.0968

Asia WGS AF: 0.0600 AC: 210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.067
DANN	Benign	0.64
PhyloP100		-0.13
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: rs2290430; hg19: chr15-60791954;