chr3-119788033-T-G

Variant names:

• chr3-119788033-T-G
• rs1403527
• NM_003889.4:c.-23+5733T>G

Variant summary

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

The NM_003889.4(NR1I2):​c.-23+5733T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,032 control chromosomes in the GnomAD database, including 42,239 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 0.72 (42239 hom., cov: 31)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978
• Publications: 13 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

ENSG00000285585 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.-23+5733T>G		intron_variant	Intron 1 of 8	ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.95+5181T>G		intron_variant	Intron 1 of 8		NP_071285.1
NR1I2	NM_033013.3	c.-23+5733T>G		intron_variant	Intron 1 of 8		NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.-23+5733T>G		intron_variant	Intron 1 of 8	1	NM_003889.4	ENSP00000377319.3
ENSG00000285585	ENST00000648112.1	c.*2-19196T>G		intron_variant	Intron 17 of 17			ENSP00000497876.1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109670 AN: 151914 Hom.: 42226 Cov.: 31

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.864

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.755

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.722 AC: 109712 AN: 152032 Hom.: 42239 Cov.: 31 AF XY: 0.731 AC XY: 54361 AN XY: 74326

African (AFR) AF: 0.430 AC: 17777 AN: 41388

American (AMR) AF: 0.833 AC: 12737 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2737 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5172 AN: 5178

South Asian (SAS) AF: 0.843 AC: 4053 AN: 4810

European-Finnish (FIN) AF: 0.872 AC: 9241 AN: 10594

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.815 AC: 55378 AN: 67988

Other (OTH) AF: 0.758 AC: 1600 AN: 2110

Alfa AF: 0.783 Hom.: 143841

Bravo AF: 0.706

Asia WGS AF: 0.897 AC: 3118 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.51
PhyloP100		-0.98
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

Other links and lift over

dbSNP: rs1403527; hg19: chr3-119506880;