chr3-119816948-C-G

Variant summary

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

The NM_003889.4(NR1I2):​c.1161-120C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,327,874 control chromosomes in the GnomAD database, including 14,338 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 0.13 ( 1508 hom., cov: 32)
Exomes 𝑓: 0.14 ( 12830 hom. )

Consequence

NR1I2
NM_003889.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.741

Publications

10 publications found
Variant links:
Genes affected
NR1I2 (HGNC:7968): (nuclear receptor subfamily 1 group I member 2) This gene product belongs to the nuclear receptor superfamily, members of which are transcription factors characterized by a ligand-binding domain and a DNA-binding domain. The encoded protein is a transcriptional regulator of the cytochrome P450 gene CYP3A4, binding to the response element of the CYP3A4 promoter as a heterodimer with the 9-cis retinoic acid receptor RXR. It is activated by a range of compounds that induce CYP3A4, including dexamethasone and rifampicin. Several alternatively spliced transcripts encoding different isoforms, some of which use non-AUG (CUG) translation initiation codon, have been described for this gene. Additional transcript variants exist, however, they have not been fully characterized. [provided by RefSeq, Jul 2008]
NR1I2 Gene-Disease associations (from GenCC):
  • pediatric lymphoma
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

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=-0.84).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NR1I2NM_003889.4 linkc.1161-120C>G intron_variant Intron 8 of 8 ENST00000393716.8 NP_003880.3 O75469-1
NR1I2NM_022002.3 linkc.1278-120C>G intron_variant Intron 8 of 8 NP_071285.1 O75469-7F1D8P9
NR1I2NM_033013.3 linkc.1050-120C>G intron_variant Intron 8 of 8 NP_148934.1 O75469-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NR1I2ENST00000393716.8 linkc.1161-120C>G intron_variant Intron 8 of 8 1 NM_003889.4 ENSP00000377319.3 O75469-1J3KPQ3
NR1I2ENST00000337940.4 linkc.1278-120C>G intron_variant Intron 8 of 8 1 ENSP00000336528.4 O75469-7
NR1I2ENST00000466380.6 linkc.1050-120C>G intron_variant Intron 8 of 8 1 ENSP00000420297.2 O75469-4H0Y8E2
NR1I2ENST00000493757.1 linkn.1293-120C>G intron_variant Intron 5 of 5 2

Frequencies

GnomAD3 genomes
AF:
0.134
AC:
20410
AN:
152000
Hom.:
1508
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.144
Gnomad AMI
AF:
0.212
Gnomad AMR
AF:
0.140
Gnomad ASJ
AF:
0.155
Gnomad EAS
AF:
0.00135
Gnomad SAS
AF:
0.0623
Gnomad FIN
AF:
0.0604
Gnomad MID
AF:
0.165
Gnomad NFE
AF:
0.151
Gnomad OTH
AF:
0.159
GnomAD4 exome
AF:
0.140
AC:
164509
AN:
1175756
Hom.:
12830
AF XY:
0.137
AC XY:
81985
AN XY:
596544
show subpopulations
African (AFR)
AF:
0.146
AC:
4046
AN:
27770
American (AMR)
AF:
0.0894
AC:
3688
AN:
41236
Ashkenazi Jewish (ASJ)
AF:
0.156
AC:
3735
AN:
23996
East Asian (EAS)
AF:
0.000267
AC:
10
AN:
37424
South Asian (SAS)
AF:
0.0672
AC:
5239
AN:
77952
European-Finnish (FIN)
AF:
0.0778
AC:
3653
AN:
46978
Middle Eastern (MID)
AF:
0.144
AC:
756
AN:
5234
European-Non Finnish (NFE)
AF:
0.158
AC:
136335
AN:
864360
Other (OTH)
AF:
0.139
AC:
7047
AN:
50806
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
7178
14357
21535
28714
35892
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
4340
8680
13020
17360
21700
<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:
0.134
AC:
20415
AN:
152118
Hom.:
1508
Cov.:
32
AF XY:
0.129
AC XY:
9590
AN XY:
74374
show subpopulations
African (AFR)
AF:
0.143
AC:
5954
AN:
41494
American (AMR)
AF:
0.140
AC:
2141
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.155
AC:
536
AN:
3468
East Asian (EAS)
AF:
0.00135
AC:
7
AN:
5178
South Asian (SAS)
AF:
0.0617
AC:
297
AN:
4814
European-Finnish (FIN)
AF:
0.0604
AC:
640
AN:
10594
Middle Eastern (MID)
AF:
0.167
AC:
49
AN:
294
European-Non Finnish (NFE)
AF:
0.151
AC:
10268
AN:
67974
Other (OTH)
AF:
0.157
AC:
331
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
879
1757
2636
3514
4393
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
222
444
666
888
1110
<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:
0.139
Hom.:
220
Bravo
AF:
0.140
Asia WGS
AF:
0.0370
AC:
130
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
1.5
DANN
Benign
0.50
PhyloP100
-0.74
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: rs11929668; hg19: chr3-119535795; API