rs2307424

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

94 publications found

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 Gene-Disease associations (from GenCC):

intellectual disability
Inheritance: AD Classification: LIMITED Submitted by: G2P

NR1I3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

GnomAD2 exomes

AF:

0.355

AC:

89158

AN:

251418

AF XY:

0.357

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 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

African (AFR)

AF:

0.136

AC:

4539

AN:

33470

American (AMR)

AF:

0.379

AC:

16948

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

8584

AN:

26130

East Asian (EAS)

AF:

0.524

AC:

20804

AN:

39696

South Asian (SAS)

AF:

0.388

AC:

33435

AN:

86242

European-Finnish (FIN)

AF:

0.315

AC:

16821

AN:

53404

Middle Eastern (MID)

AF:

0.329

AC:

1898

AN:

5766

European-Non Finnish (NFE)

AF:

0.345

AC:

383486

AN:

1111518

Other (OTH)

AF:

0.342

AC:

20630

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

16227

32454

48682

64909

81136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12442

24884

37326

49768

62210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.294

AC:

44749

AN:

152124

Hom.:

7320

Cov.:

AF XY:

0.296

AC XY:

22048

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.145

AC:

5999

AN:

41508

American (AMR)

AF:

0.347

AC:

5301

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.319

AC:

1107

AN:

3472

East Asian (EAS)

AF:

0.521

AC:

2694

AN:

5172

South Asian (SAS)

AF:

0.396

AC:

1907

AN:

4818

European-Finnish (FIN)

AF:

0.317

AC:

3361

AN:

10588

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.344

AC:

23356

AN:

67972

Other (OTH)

AF:

0.306

AC:

646

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1576

3153

4729

6306

7882

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.332

Hom.:

41568

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

(source)

DANN

Benign

0.84

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over