rs8038077

Variant names:

• chr15-60712448-T-C
• rs8038077
• NM_134261.3:c.167-33762A>G

Variant summary

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

The NM_134261.3(RORA):​c.167-33762A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,112 control chromosomes in the GnomAD database, including 3,599 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 0.17 (3599 hom., cov: 33)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.672
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 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.167-33762A>G		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.167-33762A>G		intron	N/A	ENSP00000335087.6
	RORA	ENST00000551975.5	TSL:3	n.80-33762A>G		intron	N/A	ENSP00000449482.1
	RORA	ENST00000557822.5	TSL:4	n.192-33762A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25931 AN: 151994 Hom.: 3584 Cov.: 33

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.0729

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.171 AC: 25992 AN: 152112 Hom.: 3599 Cov.: 33 AF XY: 0.171 AC XY: 12725 AN XY: 74354

African (AFR) AF: 0.375 AC: 15560 AN: 41468

American (AMR) AF: 0.102 AC: 1564 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3468

East Asian (EAS) AF: 0.194 AC: 1006 AN: 5184

South Asian (SAS) AF: 0.170 AC: 823 AN: 4828

European-Finnish (FIN) AF: 0.121 AC: 1272 AN: 10546

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.0729 AC: 4960 AN: 68012

Other (OTH) AF: 0.154 AC: 325 AN: 2110

Alfa AF: 0.104 Hom.: 2514

Bravo AF: 0.177

Asia WGS AF: 0.217 AC: 758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.80
PhyloP100		-0.67
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: rs8038077; hg19: chr15-61004647;