NM_134261.3:c.167-97635G>A

Variant names:

• chr15-60776321-C-T
• rs12438866
• NM_134261.3:c.167-97635G>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.167-97635G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,020 control chromosomes in the GnomAD database, including 24,664 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 0.56 (24664 hom., cov: 33)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• 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: 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.167-97635G>A		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1
RORA	XM_047432928.1	c.-1751-97635G>A		intron_variant	Intron 1 of 10		XP_047288884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.167-97635G>A		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85178 AN: 151902 Hom.: 24654 Cov.: 33

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.561 AC: 85220 AN: 152020 Hom.: 24664 Cov.: 33 AF XY: 0.564 AC XY: 41923 AN XY: 74310

African (AFR) AF: 0.398 AC: 16511 AN: 41470

American (AMR) AF: 0.663 AC: 10110 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2115 AN: 3470

East Asian (EAS) AF: 0.696 AC: 3591 AN: 5156

South Asian (SAS) AF: 0.614 AC: 2968 AN: 4830

European-Finnish (FIN) AF: 0.618 AC: 6531 AN: 10560

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41450 AN: 67962

Other (OTH) AF: 0.565 AC: 1192 AN: 2110

Alfa AF: 0.600 Hom.: 45969

Bravo AF: 0.561

Asia WGS AF: 0.628 AC: 2183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.38
DANN	Benign	0.81
PhyloP100		-1.3
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: rs12438866; hg19: chr15-61068520;