chr3-119810266-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003889.4(NR1I2):​c.331+72G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 1,538,278 control chromosomes in the GnomAD database, including 650,455 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 0.87 ( 58693 hom., cov: 35)
Exomes 𝑓: 0.92 ( 591762 hom. )

Consequence

NR1I2
NM_003889.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.42
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NR1I2NM_003889.4 linkuse as main transcriptc.331+72G>T intron_variant ENST00000393716.8 NP_003880.3 O75469-1
NR1I2NM_022002.3 linkuse as main transcriptc.448+72G>T intron_variant NP_071285.1 O75469-7F1D8P9
NR1I2NM_033013.3 linkuse as main transcriptc.331+72G>T intron_variant NP_148934.1 O75469-4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NR1I2ENST00000393716.8 linkuse as main transcriptc.331+72G>T intron_variant 1 NM_003889.4 ENSP00000377319.3 O75469-1J3KPQ3
NR1I2ENST00000337940.4 linkuse as main transcriptc.448+72G>T intron_variant 1 ENSP00000336528.4 O75469-7
NR1I2ENST00000466380.6 linkuse as main transcriptc.331+72G>T intron_variant 1 ENSP00000420297.2 O75469-4H0Y8E2
NR1I2ENST00000474090.1 linkuse as main transcriptn.691G>T non_coding_transcript_exon_variant 3/31

Frequencies

GnomAD3 genomes
AF:
0.874
AC:
133003
AN:
152120
Hom.:
58668
Cov.:
35
show subpopulations
Gnomad AFR
AF:
0.741
Gnomad AMI
AF:
0.906
Gnomad AMR
AF:
0.926
Gnomad ASJ
AF:
0.925
Gnomad EAS
AF:
0.901
Gnomad SAS
AF:
0.876
Gnomad FIN
AF:
0.937
Gnomad MID
AF:
0.956
Gnomad NFE
AF:
0.928
Gnomad OTH
AF:
0.883
GnomAD4 exome
AF:
0.923
AC:
1279707
AN:
1386040
Hom.:
591762
Cov.:
33
AF XY:
0.922
AC XY:
629138
AN XY:
682164
show subpopulations
Gnomad4 AFR exome
AF:
0.725
Gnomad4 AMR exome
AF:
0.952
Gnomad4 ASJ exome
AF:
0.918
Gnomad4 EAS exome
AF:
0.929
Gnomad4 SAS exome
AF:
0.873
Gnomad4 FIN exome
AF:
0.935
Gnomad4 NFE exome
AF:
0.932
Gnomad4 OTH exome
AF:
0.908
GnomAD4 genome
AF:
0.874
AC:
133079
AN:
152238
Hom.:
58693
Cov.:
35
AF XY:
0.874
AC XY:
65090
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.740
Gnomad4 AMR
AF:
0.926
Gnomad4 ASJ
AF:
0.925
Gnomad4 EAS
AF:
0.902
Gnomad4 SAS
AF:
0.876
Gnomad4 FIN
AF:
0.937
Gnomad4 NFE
AF:
0.928
Gnomad4 OTH
AF:
0.880
Alfa
AF:
0.901
Hom.:
12508
Bravo
AF:
0.869
Asia WGS
AF:
0.861
AC:
2996
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.47
DANN
Benign
0.62
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs3732356; hg19: chr3-119529113; API