3-119802208-T-C

Variant names:

• chr3-119802208-T-C
• rs13059232
• NM_003889.4:c.-22-5021T>C

Variant summary

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

The NM_003889.4(NR1I2):​c.-22-5021T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,970 control chromosomes in the GnomAD database, including 26,962 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 0.59 (26962 hom., cov: 31)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 19 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003889.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	NM_003889.4	MANE Select	c.-22-5021T>C		intron	N/A	NP_003880.3
	NR1I2	NM_022002.3		c.96-5021T>C		intron	N/A	NP_071285.1	O75469-7
	NR1I2	NM_033013.3		c.-22-5021T>C		intron	N/A	NP_148934.1	O75469-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	ENST00000393716.8	TSL:1 MANE Select	c.-22-5021T>C		intron	N/A	ENSP00000377319.3	O75469-1
	ENSG00000285585	ENST00000648112.1		c.*2-5021T>C		intron	N/A	ENSP00000497876.1
	NR1I2	ENST00000337940.4	TSL:1	c.96-5021T>C		intron	N/A	ENSP00000336528.4	O75469-7

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89789 AN: 151852 Hom.: 26939 Cov.: 31

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.591 AC: 89859 AN: 151970 Hom.: 26962 Cov.: 31 AF XY: 0.596 AC XY: 44282 AN XY: 74272

African (AFR) AF: 0.503 AC: 20842 AN: 41422

American (AMR) AF: 0.546 AC: 8327 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2324 AN: 3470

East Asian (EAS) AF: 0.641 AC: 3306 AN: 5154

South Asian (SAS) AF: 0.618 AC: 2970 AN: 4802

European-Finnish (FIN) AF: 0.699 AC: 7386 AN: 10574

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42661 AN: 67974

Other (OTH) AF: 0.577 AC: 1217 AN: 2108

Alfa AF: 0.617 Hom.: 83156

Bravo AF: 0.574

Asia WGS AF: 0.612 AC: 2130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.21
DANN	Benign	0.62
PhyloP100		-1.1
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: rs13059232; hg19: chr3-119521055;