15-60763212-C-T

Variant names:

• chr15-60763212-C-T
• rs12900122
• NM_134261.3:c.167-84526G>A

Variant summary

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

The NM_134261.3(RORA):​c.167-84526G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,234 control chromosomes in the GnomAD database, including 4,373 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 0.22 (4373 hom., cov: 27)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 12 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 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with or without epilepsy or cerebellar ataxia

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 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.167-84526G>A		intron	N/A	NP_599023.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	ENST00000335670.11	TSL:1 MANE Select	c.167-84526G>A		intron	N/A	ENSP00000335087.6
	RORA	ENST00000551975.5	TSL:3	n.80-84526G>A		intron	N/A	ENSP00000449482.1
	RORA	ENST00000557822.5	TSL:4	n.192-84526G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32784 AN: 151118 Hom.: 4365 Cov.: 27

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.217 AC: 32822 AN: 151234 Hom.: 4373 Cov.: 27 AF XY: 0.217 AC XY: 15994 AN XY: 73856

African (AFR) AF: 0.383 AC: 15736 AN: 41102

American (AMR) AF: 0.140 AC: 2135 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3464

East Asian (EAS) AF: 0.182 AC: 933 AN: 5132

South Asian (SAS) AF: 0.264 AC: 1261 AN: 4778

European-Finnish (FIN) AF: 0.175 AC: 1821 AN: 10396

Middle Eastern (MID) AF: 0.224 AC: 65 AN: 290

European-Non Finnish (NFE) AF: 0.142 AC: 9654 AN: 67842

Other (OTH) AF: 0.193 AC: 405 AN: 2098

Alfa AF: 0.139 Hom.: 652

Bravo AF: 0.217

Asia WGS AF: 0.261 AC: 903 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.41
DANN	Benign	0.73
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs12900122; hg19: chr15-61055411;