rs12488820

Variant names:

• chr3-119783222-T-C
• rs12488820
• NM_003889.4:c.-23+922T>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.-23+922T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,236 control chromosomes in the GnomAD database, including 19,993 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 0.47 (19993 hom., cov: 33)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209
• Publications: 12 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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 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+922T>C		intron	N/A	NP_003880.3
	NR1I2	NM_022002.3		c.95+370T>C		intron	N/A	NP_071285.1
	NR1I2	NM_033013.3		c.-23+922T>C		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+922T>C		intron	N/A	ENSP00000377319.3
	ENSG00000285585	ENST00000648112.1		c.*2-24007T>C		intron	N/A	ENSP00000497876.1
	NR1I2	ENST00000337940.4	TSL:1	c.95+370T>C		intron	N/A	ENSP00000336528.4

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71538 AN: 152118 Hom.: 19987 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.470 AC: 71556 AN: 152236 Hom.: 19993 Cov.: 33 AF XY: 0.478 AC XY: 35550 AN XY: 74414

African (AFR) AF: 0.151 AC: 6265 AN: 41546

American (AMR) AF: 0.548 AC: 8387 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1666 AN: 3472

East Asian (EAS) AF: 0.777 AC: 4024 AN: 5182

South Asian (SAS) AF: 0.554 AC: 2675 AN: 4832

European-Finnish (FIN) AF: 0.627 AC: 6641 AN: 10584

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40271 AN: 68008

Other (OTH) AF: 0.484 AC: 1024 AN: 2114

Alfa AF: 0.548 Hom.: 17897

Bravo AF: 0.451

Asia WGS AF: 0.656 AC: 2281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.4
DANN	Benign	0.91
PhyloP100		-0.21
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: rs12488820; hg19: chr3-119502069;