rs2307424

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005122.5(NR1I3):c.540C>T(p.Pro180Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,613,446 control chromosomes in the GnomAD database, including 97,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7320 hom., cov: 32)

Exomes 𝑓: 0.35 ( 90203 hom. )

Consequence

NR1I3
NM_005122.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.19

Variant links:

Genes affected

NR1I3 (HGNC:7969): (nuclear receptor subfamily 1 group I member 3) This gene encodes a member of the nuclear receptor superfamily, and is a key regulator of xenobiotic and endobiotic metabolism. The protein binds to DNA as a monomer or a heterodimer with the retinoid X receptor and regulates the transcription of target genes involved in drug metabolism and bilirubin clearance, such as cytochrome P450 family members. Unlike most nuclear receptors, this transcriptional regulator is constitutively active in the absence of ligand but is regulated by both agonists and inverse agonists. Ligand binding results in translocation of this protein to the nucleus, where it activates or represses target gene transcription. These ligands include bilirubin, a variety of foreign compounds, steroid hormones, and prescription drugs. In addition to drug metabolism, the CAR protein is also reported to regulate genes involved in glucose metabolism, lipid metabolism, cell proliferation, and circadian clock regulation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2020]

NR1I3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 1-161232815-G-A is Benign according to our data. Variant chr1-161232815-G-A is described in ClinVar as [Benign]. Clinvar id is 197772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1I3	NM_005122.5 link	c.540C>T	p.Pro180Pro	synonymous_variant	Exon 5 of 9	ENST00000367983.9	NP_005113.1	Q14994-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1I3	ENST00000367983.9 link	c.540C>T	p.Pro180Pro	synonymous_variant	Exon 5 of 9	1	NM_005122.5	ENSP00000356962.5		Q14994-2

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44736

AN:

152006

Hom.:

7317

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.319

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.317

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.344

Gnomad OTH

AF:

0.308

GnomAD3 exomes

AF:

0.355

AC:

89158

AN:

251418

Hom.:

16749

AF XY:

0.357

AC XY:

48535

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.386

Gnomad ASJ exome

AF:

0.327

Gnomad EAS exome

AF:

0.526

Gnomad SAS exome

AF:

0.395

Gnomad FIN exome

AF:

0.315

Gnomad NFE exome

AF:

0.347

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.347

AC:

507145

AN:

1461322

Hom.:

90203

Cov.:

AF XY:

0.348

AC XY:

252857

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.379

Gnomad4 ASJ exome

AF:

0.329

Gnomad4 EAS exome

AF:

0.524

Gnomad4 SAS exome

AF:

0.388

Gnomad4 FIN exome

AF:

0.315

Gnomad4 NFE exome

AF:

0.345

Gnomad4 OTH exome

AF:

0.342

GnomAD4 genome

AF:

0.294

AC:

44749

AN:

152124

Hom.:

7320

Cov.:

AF XY:

0.296

AC XY:

22048

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.145

Gnomad4 AMR

AF:

0.347

Gnomad4 ASJ

AF:

0.319

Gnomad4 EAS

AF:

0.521

Gnomad4 SAS

AF:

0.396

Gnomad4 FIN

AF:

0.317

Gnomad4 NFE

AF:

0.344

Gnomad4 OTH

AF:

0.306

Alfa

AF:

0.337

Hom.:

21073

Bravo

AF:

0.288

Asia WGS

AF:

0.453

AC:

1574

AN:

3478

EpiCase

AF:

0.347

EpiControl

AF:

0.346

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 02, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

NR1I3-related disorder

Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.0

DANN

Benign

0.84

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over