chr15-60750668-G-T

Variant names:

• chr15-60750668-G-T
• rs1351544
• NM_134261.3:c.167-71982C>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.167-71982C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,048 control chromosomes in the GnomAD database, including 3,438 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 0.20 (3438 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 11 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	NM_134261.3	MANE Select	c.167-71982C>A		intron	N/A	NP_599023.1	P35398-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	ENST00000335670.11	TSL:1 MANE Select	c.167-71982C>A		intron	N/A	ENSP00000335087.6	P35398-2
	RORA	ENST00000551975.5	TSL:3	n.80-71982C>A		intron	N/A	ENSP00000449482.1	H0YII6
	RORA	ENST00000557822.5	TSL:4	n.192-71982C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30039 AN: 151930 Hom.: 3433 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.198 AC: 30067 AN: 152048 Hom.: 3438 Cov.: 32 AF XY: 0.198 AC XY: 14705 AN XY: 74334

African (AFR) AF: 0.318 AC: 13177 AN: 41476

American (AMR) AF: 0.129 AC: 1977 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 586 AN: 3472

East Asian (EAS) AF: 0.216 AC: 1111 AN: 5154

South Asian (SAS) AF: 0.258 AC: 1240 AN: 4814

European-Finnish (FIN) AF: 0.169 AC: 1788 AN: 10558

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9633 AN: 67968

Other (OTH) AF: 0.177 AC: 373 AN: 2110

Alfa AF: 0.152 Hom.: 2433

Bravo AF: 0.195

Asia WGS AF: 0.252 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.034
DANN	Benign	0.18
PhyloP100		-2.2
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: rs1351544; hg19: chr15-61042867;