3-119784198-C-T

Variant names:

• chr3-119784198-C-T
• rs2472671
• NM_003889.4:c.-23+1898C>T

Variant summary

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

The NM_022002.3(NR1I2):​c.95+1346C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 152,178 control chromosomes in the GnomAD database, including 42,244 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 (42244 hom., cov: 33)
• Consequence: NR1I2 NM_022002.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• Publications: 10 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022002.3. 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.-23+1898C>T		intron	N/A	NP_003880.3
	NR1I2	NM_022002.3		c.95+1346C>T		intron	N/A	NP_071285.1
	NR1I2	NM_033013.3		c.-23+1898C>T		intron	N/A	NP_148934.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	ENST00000393716.8	TSL:1 MANE Select	c.-23+1898C>T		intron	N/A	ENSP00000377319.3
	ENSG00000285585	ENST00000648112.1		c.*2-23031C>T		intron	N/A	ENSP00000497876.1
	NR1I2	ENST00000337940.4	TSL:1	c.95+1346C>T		intron	N/A	ENSP00000336528.4

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109697 AN: 152060 Hom.: 42231 Cov.: 33

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.864

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.754

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

GnomAD4 genome AF: 0.721 AC: 109739 AN: 152178 Hom.: 42244 Cov.: 33 AF XY: 0.731 AC XY: 54388 AN XY: 74406

African (AFR) AF: 0.428 AC: 17757 AN: 41468

American (AMR) AF: 0.834 AC: 12752 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2735 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5175 AN: 5182

South Asian (SAS) AF: 0.843 AC: 4066 AN: 4824

European-Finnish (FIN) AF: 0.872 AC: 9248 AN: 10606

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

European-Non Finnish (NFE) AF: 0.814 AC: 55390 AN: 68012

Other (OTH) AF: 0.757 AC: 1599 AN: 2112

Alfa AF: 0.776 Hom.: 56738

Bravo AF: 0.706

Asia WGS AF: 0.897 AC: 3120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.72
PhyloP100		-0.18
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: rs2472671; hg19: chr3-119503045;