3-119782460-G-A

Variant names:

• chr3-119782460-G-A
• rs2276706
• NM_003889.4:c.-23+160G>A

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+160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 148,734 control chromosomes in the GnomAD database, including 9,439 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 0.35 (9439 hom., cov: 29)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 22 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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	NM_003889.4	MANE Select	c.-23+160G>A		intron	N/A	NP_003880.3
	NR1I2	NM_033013.3		c.-23+160G>A		intron	N/A	NP_148934.1
	NR1I2	NM_022002.3		c.-298G>A		upstream_gene	N/A	NP_071285.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	ENST00000393716.8	TSL:1 MANE Select	c.-23+160G>A		intron	N/A	ENSP00000377319.3
	ENSG00000285585	ENST00000648112.1		c.*2-24769G>A		intron	N/A	ENSP00000497876.1
	NR1I2	ENST00000466380.6	TSL:1	c.-23+160G>A		intron	N/A	ENSP00000420297.2

Frequencies

GnomAD3 genomes AF: 0.354 AC: 52622 AN: 148640 Hom.: 9439 Cov.: 29

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.354 AC: 52640 AN: 148734 Hom.: 9439 Cov.: 29 AF XY: 0.352 AC XY: 25500 AN XY: 72414

African (AFR) AF: 0.288 AC: 11589 AN: 40282

American (AMR) AF: 0.371 AC: 5575 AN: 15034

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1721 AN: 3444

East Asian (EAS) AF: 0.224 AC: 1137 AN: 5080

South Asian (SAS) AF: 0.373 AC: 1753 AN: 4698

European-Finnish (FIN) AF: 0.367 AC: 3613 AN: 9836

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 25961 AN: 67088

Other (OTH) AF: 0.361 AC: 748 AN: 2070

Alfa AF: 0.365 Hom.: 6985

Bravo AF: 0.348

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.3
DANN	Benign	0.72
PhyloP100		-1.1
PromoterAI		-0.0098	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2276706; hg19: chr3-119501307;