rs1054190

Variant names:

• chr3-119817871-C-T
• rs1054190
• NM_003889.4:c.*659C>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.*659C>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 0.116 in 988,214 control chromosomes in the GnomAD database, including 7,156 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 0.090 (757 hom., cov: 32)
  • Exomes 𝑓: 0.12 (6399 hom.)
• Consequence: NR1I2 NM_003889.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 41 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.*659C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.*659C>T		3_prime_UTR_variant	Exon 9 of 9		NP_071285.1
NR1I2	NM_033013.3	c.*659C>T		3_prime_UTR_variant	Exon 9 of 9		NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.*659C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_003889.4	ENSP00000377319.3
NR1I2	ENST00000337940.4	c.*659C>T		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000336528.4
NR1I2	ENST00000466380.6	c.*659C>T		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000420297.2
NR1I2	ENST00000493757.1	n.2096C>T		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes AF: 0.0901 AC: 13687 AN: 151974 Hom.: 758 Cov.: 32

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0399

Gnomad FIN AF: 0.0525

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.121 AC: 101184 AN: 836122 Hom.: 6399 Cov.: 23 AF XY: 0.122 AC XY: 46964 AN XY: 386282

African (AFR) AF: 0.0529 AC: 836 AN: 15794

American (AMR) AF: 0.0682 AC: 141 AN: 2068

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 757 AN: 5164

East Asian (EAS) AF: 0.00106 AC: 4 AN: 3784

South Asian (SAS) AF: 0.0444 AC: 743 AN: 16742

European-Finnish (FIN) AF: 0.0638 AC: 18 AN: 282

Middle Eastern (MID) AF: 0.109 AC: 176 AN: 1620

European-Non Finnish (NFE) AF: 0.125 AC: 95633 AN: 763268

Other (OTH) AF: 0.105 AC: 2876 AN: 27400

GnomAD4 genome AF: 0.0900 AC: 13685 AN: 152092 Hom.: 757 Cov.: 32 AF XY: 0.0866 AC XY: 6441 AN XY: 74354

African (AFR) AF: 0.0549 AC: 2279 AN: 41478

American (AMR) AF: 0.0998 AC: 1525 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3468

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5176

South Asian (SAS) AF: 0.0393 AC: 189 AN: 4810

European-Finnish (FIN) AF: 0.0525 AC: 554 AN: 10558

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8228 AN: 68006

Other (OTH) AF: 0.113 AC: 238 AN: 2108

Alfa AF: 0.110 Hom.: 3450

Bravo AF: 0.0930

Asia WGS AF: 0.0240 AC: 82 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.60
DANN	Benign	0.66
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: rs1054190; hg19: chr3-119536718;