chr15-61102033-A-G

Position:

• chr15-61102033-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000335670.11(RORA):​c.166+127020T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,826 control chromosomes in the GnomAD database, including 28,952 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 0.62 (28952 hom., cov: 30)
• Consequence: RORA ENST00000335670.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435

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]

LOC107984805 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RORA	NM_134261.3	c.166+127020T>C		intron_variant		ENST00000335670.11	NP_599023.1
LOC107984805	XR_007064660.1	n.33545T>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.166+127020T>C		intron_variant		1	NM_134261.3	ENSP00000335087

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93340 AN: 151708 Hom.: 28919 Cov.: 30

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.615 AC: 93418 AN: 151826 Hom.: 28952 Cov.: 30 AF XY: 0.619 AC XY: 45929 AN XY: 74170

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.699

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.636

Alfa AF: 0.611 Hom.: 8110

Bravo AF: 0.622

Asia WGS AF: 0.640 AC: 2229 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	4.0
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs893287; hg19: chr15-61394232; COSMIC: COSV59546573;