chr15-60918990-A-T

Variant names:

• chr15-60918990-A-T
• rs8028646
• NM_134261.3:c.167-240304T>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.167-240304T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 152,062 control chromosomes in the GnomAD database, including 36,121 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 0.68 (36121 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 6 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 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.167-240304T>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.167-240304T>A		intron	N/A	ENSP00000335087.6
	RORA	ENST00000551975.5	TSL:3	n.80-240304T>A		intron	N/A	ENSP00000449482.1
	RORA	ENST00000557822.5	TSL:4	n.192-240304T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103672 AN: 151944 Hom.: 36099 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.701

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

GnomAD4 genome AF: 0.682 AC: 103742 AN: 152062 Hom.: 36121 Cov.: 32 AF XY: 0.687 AC XY: 51087 AN XY: 74328

African (AFR) AF: 0.546 AC: 22627 AN: 41454

American (AMR) AF: 0.778 AC: 11882 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2239 AN: 3470

East Asian (EAS) AF: 0.873 AC: 4510 AN: 5164

South Asian (SAS) AF: 0.611 AC: 2947 AN: 4820

European-Finnish (FIN) AF: 0.781 AC: 8262 AN: 10582

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.721 AC: 48991 AN: 67974

Other (OTH) AF: 0.703 AC: 1484 AN: 2112

Alfa AF: 0.641 Hom.: 2194

Bravo AF: 0.679

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.81
PhyloP100		0.25
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: rs8028646; hg19: chr15-61211189;