3-119817734-C-T

Variant names:

• chr3-119817734-C-T
• rs3732360
• NM_003889.4:c.*522C>T

Variant summary

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

The NM_003889.4(NR1I2):​c.*522C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 1,028,112 control chromosomes in the GnomAD database, including 265,513 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 0.61 (30214 hom., cov: 32)
  • Exomes 𝑓: 0.73 (235299 hom.)
• Consequence: NR1I2 NM_003889.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 61 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.726 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.*522C>T		3_prime_UTR	Exon 9 of 9	NP_003880.3
	NR1I2	NM_022002.3		c.*522C>T		3_prime_UTR	Exon 9 of 9	NP_071285.1	O75469-7
	NR1I2	NM_033013.3		c.*522C>T		3_prime_UTR	Exon 9 of 9	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.*522C>T		3_prime_UTR	Exon 9 of 9	ENSP00000377319.3	O75469-1
	NR1I2	ENST00000337940.4	TSL:1	c.*522C>T		3_prime_UTR	Exon 9 of 9	ENSP00000336528.4	O75469-7
	NR1I2	ENST00000466380.6	TSL:1	c.*522C>T		3_prime_UTR	Exon 9 of 9	ENSP00000420297.2	O75469-4

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92355 AN: 151942 Hom.: 30210 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.636

GnomAD4 exome AF: 0.729 AC: 638654 AN: 876052 Hom.: 235299 Cov.: 37 AF XY: 0.729 AC XY: 296541 AN XY: 406662

African (AFR) AF: 0.329 AC: 5858 AN: 17794

American (AMR) AF: 0.731 AC: 3391 AN: 4638

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 4520 AN: 6078

East Asian (EAS) AF: 0.434 AC: 2997 AN: 6912

South Asian (SAS) AF: 0.572 AC: 12025 AN: 21028

European-Finnish (FIN) AF: 0.661 AC: 972 AN: 1470

Middle Eastern (MID) AF: 0.671 AC: 1193 AN: 1778

European-Non Finnish (NFE) AF: 0.747 AC: 587549 AN: 786900

Other (OTH) AF: 0.684 AC: 20149 AN: 29454

GnomAD4 genome AF: 0.608 AC: 92394 AN: 152060 Hom.: 30214 Cov.: 32 AF XY: 0.605 AC XY: 44992 AN XY: 74320

African (AFR) AF: 0.362 AC: 15010 AN: 41440

American (AMR) AF: 0.706 AC: 10803 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2593 AN: 3472

East Asian (EAS) AF: 0.426 AC: 2196 AN: 5154

South Asian (SAS) AF: 0.551 AC: 2655 AN: 4816

European-Finnish (FIN) AF: 0.673 AC: 7113 AN: 10570

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49731 AN: 67996

Other (OTH) AF: 0.634 AC: 1340 AN: 2112

Alfa AF: 0.696 Hom.: 160633

Bravo AF: 0.603

Asia WGS AF: 0.484 AC: 1687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.27
DANN	Benign	0.72
PhyloP100		-1.4
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: rs3732360; hg19: chr3-119536581;