rs341408

Variant names:

• chr15-60849491-T-C
• rs341408
• NM_134261.3:c.167-170805A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-60849491-T-C
• chr15-60849491-T-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.167-170805A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,060 control chromosomes in the GnomAD database, including 25,160 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 0.57 (25160 hom., cov: 32)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 9 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)

LOC124903500 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.167-170805A>G		intron_variant	Intron 1 of 10	ENST00000335670.11	NP_599023.1
LOC124903500	XR_007064666.1	n.2012A>G		non_coding_transcript_exon_variant	Exon 2 of 2
RORA	XM_047432928.1	c.-1751-170805A>G		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.167-170805A>G		intron_variant	Intron 1 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86833 AN: 151942 Hom.: 25143 Cov.: 32

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.571 AC: 86881 AN: 152060 Hom.: 25160 Cov.: 32 AF XY: 0.574 AC XY: 42671 AN XY: 74338

African (AFR) AF: 0.493 AC: 20413 AN: 41444

American (AMR) AF: 0.559 AC: 8544 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2244 AN: 3468

East Asian (EAS) AF: 0.717 AC: 3706 AN: 5172

South Asian (SAS) AF: 0.691 AC: 3331 AN: 4824

European-Finnish (FIN) AF: 0.617 AC: 6523 AN: 10570

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40230 AN: 67976

Other (OTH) AF: 0.599 AC: 1267 AN: 2116

Alfa AF: 0.588 Hom.: 50448

Bravo AF: 0.564

Asia WGS AF: 0.680 AC: 2363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.057
DANN	Benign	0.29
PhyloP100		-2.0
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: rs341408; hg19: chr15-61141690;