rs341401

Variant names:

• chr15-60840646-G-A
• rs341401
• NM_134261.3:c.167-161960C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-60840646-G-A
• chr15-60840646-G-C
• chr15-60840646-G-T

Variant summary

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

The NM_134261.3(RORA):​c.167-161960C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 152,102 control chromosomes in the GnomAD database, including 16,407 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 0.46 (16407 hom., cov: 33)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 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.167-161960C>T		intron	N/A	NP_599023.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORA	ENST00000335670.11	TSL:1 MANE Select	c.167-161960C>T		intron	N/A	ENSP00000335087.6
	RORA	ENST00000551975.5	TSL:3	n.80-161960C>T		intron	N/A	ENSP00000449482.1
	RORA	ENST00000557822.5	TSL:4	n.192-161960C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69966 AN: 151984 Hom.: 16375 Cov.: 33

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.461 AC: 70050 AN: 152102 Hom.: 16407 Cov.: 33 AF XY: 0.467 AC XY: 34694 AN XY: 74340

African (AFR) AF: 0.445 AC: 18462 AN: 41490

American (AMR) AF: 0.531 AC: 8114 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1565 AN: 3470

East Asian (EAS) AF: 0.616 AC: 3185 AN: 5168

South Asian (SAS) AF: 0.422 AC: 2035 AN: 4818

European-Finnish (FIN) AF: 0.476 AC: 5033 AN: 10574

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30187 AN: 67974

Other (OTH) AF: 0.457 AC: 966 AN: 2114

Alfa AF: 0.434 Hom.: 10321

Bravo AF: 0.466

Asia WGS AF: 0.541 AC: 1882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.7
DANN	Benign	0.69
PhyloP100		0.36
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: rs341401; hg19: chr15-61132845;