chr3-119817227-G-A

Variant names:

• chr3-119817227-G-A
• rs3732358
• NM_003889.4:c.*15G>A

Variant summary

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

The NM_022002.3(NR1I2):​c.*15G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00533 in 1,613,280 control chromosomes in the GnomAD database, including 258 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 0.023 (126 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (132 hom.)
• Consequence: NR1I2 NM_022002.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0778 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	NM_003889.4	MANE Select	c.*15G>A		3_prime_UTR	Exon 9 of 9	NP_003880.3
	NR1I2	NM_022002.3		c.*15G>A		3_prime_UTR	Exon 9 of 9	NP_071285.1
	NR1I2	NM_033013.3		c.*15G>A		3_prime_UTR	Exon 9 of 9	NP_148934.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	ENST00000393716.8	TSL:1 MANE Select	c.*15G>A		3_prime_UTR	Exon 9 of 9	ENSP00000377319.3
	NR1I2	ENST00000337940.4	TSL:1	c.*15G>A		3_prime_UTR	Exon 9 of 9	ENSP00000336528.4
	NR1I2	ENST00000466380.6	TSL:1	c.*15G>A		3_prime_UTR	Exon 9 of 9	ENSP00000420297.2

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3553 AN: 152110 Hom.: 123 Cov.: 32

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00766

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.00436

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.00692 AC: 1734 AN: 250676 AF XY: 0.00556

Gnomad AFR exome AF: 0.0848

Gnomad AMR exome AF: 0.00298

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00228

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000378

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00345 AC: 5034 AN: 1461052 Hom.: 132 Cov.: 30 AF XY: 0.00321 AC XY: 2336 AN XY: 726862

African (AFR) AF: 0.0813 AC: 2723 AN: 33480

American (AMR) AF: 0.00376 AC: 168 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0261 AC: 1038 AN: 39700

South Asian (SAS) AF: 0.00524 AC: 452 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52652

Middle Eastern (MID) AF: 0.00555 AC: 32 AN: 5766

European-Non Finnish (NFE) AF: 0.000192 AC: 213 AN: 1111964

Other (OTH) AF: 0.00676 AC: 408 AN: 60378

GnomAD4 genome AF: 0.0234 AC: 3569 AN: 152228 Hom.: 126 Cov.: 32 AF XY: 0.0231 AC XY: 1723 AN XY: 74430

African (AFR) AF: 0.0801 AC: 3326 AN: 41520

American (AMR) AF: 0.00765 AC: 117 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0100 AC: 52 AN: 5182

South Asian (SAS) AF: 0.00437 AC: 21 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68014

Other (OTH) AF: 0.0156 AC: 33 AN: 2112

Alfa AF: 0.0110 Hom.: 132

Bravo AF: 0.0269

Asia WGS AF: 0.0150 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.5
DANN	Benign	0.73
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3732358; hg19: chr3-119536074;