15-60500743-G-A

Variant names:

• chr15-60500743-G-A
• rs7183916
• NM_134261.3:c.1294+216C>T

Variant summary

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

The NM_134261.3(RORA):​c.1294+216C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,094 control chromosomes in the GnomAD database, including 43,739 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 0.75 (43739 hom., cov: 31)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384
• Publications: 9 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	NM_134261.3	MANE Select	c.1294+216C>T		intron	N/A	NP_599023.1
	RORA	NM_134260.3		c.1393+216C>T		intron	N/A	NP_599022.1
	RORA	NM_002943.4		c.1369+216C>T		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.1294+216C>T		intron	N/A	ENSP00000335087.6
	RORA	ENST00000261523.9	TSL:1	c.1393+216C>T		intron	N/A	ENSP00000261523.5
	RORA	ENST00000309157.8	TSL:1	c.1369+216C>T		intron	N/A	ENSP00000309753.3

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113843 AN: 151976 Hom.: 43706 Cov.: 31

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.749 AC: 113930 AN: 152094 Hom.: 43739 Cov.: 31 AF XY: 0.756 AC XY: 56188 AN XY: 74366

African (AFR) AF: 0.567 AC: 23490 AN: 41428

American (AMR) AF: 0.795 AC: 12157 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2729 AN: 3472

East Asian (EAS) AF: 0.949 AC: 4926 AN: 5188

South Asian (SAS) AF: 0.894 AC: 4309 AN: 4820

European-Finnish (FIN) AF: 0.856 AC: 9069 AN: 10592

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.805 AC: 54690 AN: 67978

Other (OTH) AF: 0.760 AC: 1606 AN: 2112

Alfa AF: 0.781 Hom.: 68427

Bravo AF: 0.736

Asia WGS AF: 0.899 AC: 3122 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.83
DANN	Benign	0.56
PhyloP100		-0.38
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: rs7183916; hg19: chr15-60792942;