chr15-60618351-C-T

Position:

• chr15-60618351-C-T

Variant summary

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

The NM_134261.3(RORA):​c.196+60306G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,204 control chromosomes in the GnomAD database, including 1,930 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 0.15 (1930 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORA	NM_134261.3	c.196+60306G>A		intron_variant		ENST00000335670.11	NP_599023.1
RORA-AS1	NR_120342.1	n.568-12093C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.196+60306G>A		intron_variant		1	NM_134261.3	ENSP00000335087
RORA-AS1	ENST00000559824.5	n.568-12093C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23063 AN: 152086 Hom.: 1933 Cov.: 32

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0758

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.152 AC: 23062 AN: 152204 Hom.: 1930 Cov.: 32 AF XY: 0.152 AC XY: 11321 AN XY: 74410

Gnomad4 AFR AF: 0.0765

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.0757

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.189

Alfa AF: 0.186 Hom.: 5939

Bravo AF: 0.149

Asia WGS AF: 0.110 AC: 382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.5
DANN	Benign	0.62

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: rs3784609; hg19: chr15-60910550;