NM_134261.3:c.197-24720C>T

Variant names:

• chr15-60556571-G-A
• rs10431796
• NM_134261.3:c.197-24720C>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.197-24720C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,012 control chromosomes in the GnomAD database, including 12,091 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 0.38 (12091 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.33
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.197-24720C>T		intron_variant	Intron 2 of 10	ENST00000335670.11	NP_599023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.197-24720C>T		intron_variant	Intron 2 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57568 AN: 151894 Hom.: 12085 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.379 AC: 57584 AN: 152012 Hom.: 12091 Cov.: 32 AF XY: 0.387 AC XY: 28767 AN XY: 74322

African (AFR) AF: 0.202 AC: 8359 AN: 41468

American (AMR) AF: 0.404 AC: 6170 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1298 AN: 3470

East Asian (EAS) AF: 0.746 AC: 3863 AN: 5178

South Asian (SAS) AF: 0.484 AC: 2328 AN: 4814

European-Finnish (FIN) AF: 0.534 AC: 5639 AN: 10556

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28571 AN: 67926

Other (OTH) AF: 0.366 AC: 773 AN: 2114

Alfa AF: 0.404 Hom.: 54820

Bravo AF: 0.356

Asia WGS AF: 0.591 AC: 2054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.039
DANN	Benign	0.22
PhyloP100		-3.3
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: rs10431796; hg19: chr15-60848770; COSMIC: COSV55038940; COSMIC: COSV55038940;