NM_005122.5:c.239-1089T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005122.5(NR1I3):​c.239-1089T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 151,446 control chromosomes in the GnomAD database, including 15,741 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 0.45 ( 15741 hom., cov: 31)

Consequence

NR1I3
NM_005122.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.504

Publications

30 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NR1I3NM_005122.5 linkc.239-1089T>C intron_variant Intron 3 of 8 ENST00000367983.9 NP_005113.1 Q14994-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NR1I3ENST00000367983.9 linkc.239-1089T>C intron_variant Intron 3 of 8 1 NM_005122.5 ENSP00000356962.5 Q14994-2

Frequencies

GnomAD3 genomes
AF:
0.453
AC:
68544
AN:
151330
Hom.:
15712
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.488
Gnomad AMI
AF:
0.451
Gnomad AMR
AF:
0.461
Gnomad ASJ
AF:
0.374
Gnomad EAS
AF:
0.553
Gnomad SAS
AF:
0.472
Gnomad FIN
AF:
0.464
Gnomad MID
AF:
0.399
Gnomad NFE
AF:
0.423
Gnomad OTH
AF:
0.445
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.453
AC:
68627
AN:
151446
Hom.:
15741
Cov.:
31
AF XY:
0.456
AC XY:
33773
AN XY:
74032
show subpopulations
African (AFR)
AF:
0.488
AC:
20211
AN:
41418
American (AMR)
AF:
0.462
AC:
7058
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
0.374
AC:
1275
AN:
3410
East Asian (EAS)
AF:
0.554
AC:
2860
AN:
5166
South Asian (SAS)
AF:
0.472
AC:
2267
AN:
4804
European-Finnish (FIN)
AF:
0.464
AC:
4894
AN:
10538
Middle Eastern (MID)
AF:
0.425
AC:
125
AN:
294
European-Non Finnish (NFE)
AF:
0.423
AC:
28600
AN:
67580
Other (OTH)
AF:
0.451
AC:
947
AN:
2100
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1884
3769
5653
7538
9422
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
626
1252
1878
2504
3130
<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:
0.434
Hom.:
19634
Bravo
AF:
0.459

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
2.3
DANN
Benign
0.45
PhyloP100
0.50
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

Publications

Other links and lift over

dbSNP: rs3003596; hg19: chr1-161204217; COSMIC: COSV107457374; COSMIC: COSV107457374; API