ENST00000474090.1:n.691G>T

Variant names:

• chr3-119810266-G-T
• rs3732356
• ENST00000474090.1:n.691G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000474090.1(NR1I2):​n.691G>T variant causes a non coding transcript exon 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 ENST00000474090.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42
• Publications: 18 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 lymphoma

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000474090.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	NM_003889.4	MANE Select	c.331+72G>T		intron	N/A	NP_003880.3
	NR1I2	NM_022002.3		c.448+72G>T		intron	N/A	NP_071285.1
	NR1I2	NM_033013.3		c.331+72G>T		intron	N/A	NP_148934.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	ENST00000474090.1	TSL:1	n.691G>T		non_coding_transcript_exon	Exon 3 of 3
	NR1I2	ENST00000393716.8	TSL:1 MANE Select	c.331+72G>T		intron	N/A	ENSP00000377319.3
	NR1I2	ENST00000337940.4	TSL:1	c.448+72G>T		intron	N/A	ENSP00000336528.4

Frequencies

GnomAD3 genomes AF: 0.874 AC: 133003 AN: 152120 Hom.: 58668 Cov.: 35

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

African (AFR) AF: 0.725 AC: 22666 AN: 31254

American (AMR) AF: 0.952 AC: 33347 AN: 35016

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 22660 AN: 24692

East Asian (EAS) AF: 0.929 AC: 33026 AN: 35542

South Asian (SAS) AF: 0.873 AC: 68330 AN: 78230

European-Finnish (FIN) AF: 0.935 AC: 43631 AN: 46662

Middle Eastern (MID) AF: 0.906 AC: 4882 AN: 5388

European-Non Finnish (NFE) AF: 0.932 AC: 999031 AN: 1071846

Other (OTH) AF: 0.908 AC: 52134 AN: 57410

GnomAD4 genome AF: 0.874 AC: 133079 AN: 152238 Hom.: 58693 Cov.: 35 AF XY: 0.874 AC XY: 65090 AN XY: 74442

African (AFR) AF: 0.740 AC: 30750 AN: 41528

American (AMR) AF: 0.926 AC: 14180 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 3211 AN: 3472

East Asian (EAS) AF: 0.902 AC: 4659 AN: 5164

South Asian (SAS) AF: 0.876 AC: 4228 AN: 4826

European-Finnish (FIN) AF: 0.937 AC: 9950 AN: 10616

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.928 AC: 63134 AN: 67998

Other (OTH) AF: 0.880 AC: 1860 AN: 2114

Alfa AF: 0.896 Hom.: 30087

Bravo AF: 0.869

Asia WGS AF: 0.861 AC: 2996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.47
DANN	Benign	0.62
PhyloP100		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3732356; hg19: chr3-119529113;