rs1054191

Variant names:

• chr3-119818050-G-A
• rs1054191
• NM_003889.4:c.*838G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-119818050-G-A
• chr3-119818050-G-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.*838G>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 0.152 in 985,362 control chromosomes in the GnomAD database, including 11,839 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 0.13 (1478 hom., cov: 33)
  • Exomes 𝑓: 0.16 (10361 hom.)
• Consequence: NR1I2 NM_003889.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479
• Publications: 29 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.*838G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.*838G>A		3_prime_UTR_variant	Exon 9 of 9		NP_071285.1
NR1I2	NM_033013.3	c.*838G>A		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.*838G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_003889.4	ENSP00000377319.3
NR1I2	ENST00000337940.4	c.*838G>A		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000336528.4
NR1I2	ENST00000466380.6	c.*838G>A		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000420297.2
NR1I2	ENST00000493757.1	n.2275G>A		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20207 AN: 152018 Hom.: 1478 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0621

Gnomad FIN AF: 0.0604

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.155 AC: 129434 AN: 833226 Hom.: 10361 Cov.: 33 AF XY: 0.156 AC XY: 59888 AN XY: 384786

African (AFR) AF: 0.142 AC: 2244 AN: 15786

American (AMR) AF: 0.108 AC: 106 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 844 AN: 5152

East Asian (EAS) AF: 0.00137 AC: 5 AN: 3640

South Asian (SAS) AF: 0.0654 AC: 1077 AN: 16460

European-Finnish (FIN) AF: 0.0828 AC: 28 AN: 338

Middle Eastern (MID) AF: 0.140 AC: 227 AN: 1620

European-Non Finnish (NFE) AF: 0.159 AC: 121116 AN: 761940

Other (OTH) AF: 0.139 AC: 3787 AN: 27306

GnomAD4 genome AF: 0.133 AC: 20214 AN: 152136 Hom.: 1478 Cov.: 33 AF XY: 0.128 AC XY: 9485 AN XY: 74384

African (AFR) AF: 0.141 AC: 5863 AN: 41488

American (AMR) AF: 0.136 AC: 2080 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 536 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5180

South Asian (SAS) AF: 0.0615 AC: 297 AN: 4826

European-Finnish (FIN) AF: 0.0604 AC: 641 AN: 10604

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10227 AN: 67980

Other (OTH) AF: 0.156 AC: 329 AN: 2108

Alfa AF: 0.142 Hom.: 3191

Bravo AF: 0.138

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.97
DANN	Benign	0.31
PhyloP100		-0.48
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: rs1054191; hg19: chr3-119536897;