chr15-60601232-T-C

Position:

• chr15-60601232-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_134261.3(RORA):​c.197-69381A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,234 control chromosomes in the GnomAD database, including 1,940 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 (1940 hom., cov: 33)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORA	NM_134261.3	c.197-69381A>G		intron_variant		ENST00000335670.11	NP_599023.1
RORA-AS1	NR_120342.1	n.567+175T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.197-69381A>G		intron_variant		1	NM_134261.3	ENSP00000335087
RORA-AS1	ENST00000559824.5	n.567+175T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22675 AN: 152114 Hom.: 1946 Cov.: 33

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.149 AC: 22669 AN: 152234 Hom.: 1940 Cov.: 33 AF XY: 0.154 AC XY: 11427 AN XY: 74436

Gnomad4 AFR AF: 0.0530

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.173

Alfa AF: 0.170 Hom.: 1311

Bravo AF: 0.144

Asia WGS AF: 0.204 AC: 707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Benign	0.83

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: rs4774370; hg19: chr15-60893431;