chr3-119811586-C-A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7
The NM_003889.4(NR1I2):c.379C>A(p.Arg127Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,522 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
NR1I2
NM_003889.4 synonymous
NM_003889.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.74
Publications
3 publications found
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 lymphomaInheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.22).
BP7
Synonymous conserved (PhyloP=2.74 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| NR1I2 | NM_003889.4 | c.379C>A | p.Arg127Arg | synonymous_variant | Exon 4 of 9 | ENST00000393716.8 | NP_003880.3 | |
| NR1I2 | NM_022002.3 | c.496C>A | p.Arg166Arg | synonymous_variant | Exon 4 of 9 | NP_071285.1 | ||
| NR1I2 | NM_033013.3 | c.379C>A | p.Arg127Arg | synonymous_variant | Exon 4 of 9 | NP_148934.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| NR1I2 | ENST00000393716.8 | c.379C>A | p.Arg127Arg | synonymous_variant | Exon 4 of 9 | 1 | NM_003889.4 | ENSP00000377319.3 | ||
| NR1I2 | ENST00000337940.4 | c.496C>A | p.Arg166Arg | synonymous_variant | Exon 4 of 9 | 1 | ENSP00000336528.4 | |||
| NR1I2 | ENST00000466380.6 | c.379C>A | p.Arg127Arg | synonymous_variant | Exon 4 of 9 | 1 | ENSP00000420297.2 | |||
| NR1I2 | ENST00000493757.1 | n.511C>A | non_coding_transcript_exon_variant | Exon 1 of 6 | 2 |
Frequencies
GnomAD3 genomes 0.0000132 AC: 2AN: 152078Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152078
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
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Gnomad ASJ
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Gnomad EAS
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Gnomad SAS
AF:
Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000120 AC: 3AN: 249626 AF XY: 0.00000740 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
249626
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461444Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726990 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1461444
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
726990
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33474
American (AMR)
AF:
AC:
0
AN:
44674
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26122
East Asian (EAS)
AF:
AC:
4
AN:
39688
South Asian (SAS)
AF:
AC:
0
AN:
86164
European-Finnish (FIN)
AF:
AC:
0
AN:
53390
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111794
Other (OTH)
AF:
AC:
0
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.463
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000132 AC: 2AN: 152078Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74274 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
152078
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74274
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41384
American (AMR)
AF:
AC:
0
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
2
AN:
5180
South Asian (SAS)
AF:
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68018
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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