chr3-119818444-T-C

Variant names:

• chr3-119818444-T-C
• rs3814058
• NM_003889.4:c.*1232T>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.*1232T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 983,836 control chromosomes in the GnomAD database, including 22,029 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 0.28 (7128 hom., cov: 32)
  • Exomes 𝑓: 0.18 (14901 hom.)
• Consequence: NR1I2 NM_003889.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• Publications: 37 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 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.*1232T>C		3_prime_UTR	Exon 9 of 9	NP_003880.3
	NR1I2	NM_022002.3		c.*1232T>C		3_prime_UTR	Exon 9 of 9	NP_071285.1
	NR1I2	NM_033013.3		c.*1232T>C		3_prime_UTR	Exon 9 of 9	NP_148934.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	ENST00000393716.8	TSL:1 MANE Select	c.*1232T>C		3_prime_UTR	Exon 9 of 9	ENSP00000377319.3
	NR1I2	ENST00000337940.4	TSL:1	c.*1232T>C		3_prime_UTR	Exon 9 of 9	ENSP00000336528.4
	NR1I2	ENST00000466380.6	TSL:1	c.*1232T>C		3_prime_UTR	Exon 9 of 9	ENSP00000420297.2

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42556 AN: 151804 Hom.: 7112 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.253

GnomAD4 exome AF: 0.181 AC: 150757 AN: 831914 Hom.: 14901 Cov.: 29 AF XY: 0.181 AC XY: 69528 AN XY: 384176

African (AFR) AF: 0.471 AC: 7403 AN: 15732

American (AMR) AF: 0.200 AC: 196 AN: 982

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 1004 AN: 5146

East Asian (EAS) AF: 0.486 AC: 1758 AN: 3618

South Asian (SAS) AF: 0.278 AC: 4571 AN: 16422

European-Finnish (FIN) AF: 0.225 AC: 62 AN: 276

Middle Eastern (MID) AF: 0.238 AC: 385 AN: 1616

European-Non Finnish (NFE) AF: 0.170 AC: 129475 AN: 760878

Other (OTH) AF: 0.217 AC: 5903 AN: 27244

GnomAD4 genome AF: 0.281 AC: 42620 AN: 151922 Hom.: 7128 Cov.: 32 AF XY: 0.282 AC XY: 20967 AN XY: 74260

African (AFR) AF: 0.449 AC: 18559 AN: 41372

American (AMR) AF: 0.220 AC: 3354 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3472

East Asian (EAS) AF: 0.486 AC: 2507 AN: 5162

South Asian (SAS) AF: 0.291 AC: 1401 AN: 4818

European-Finnish (FIN) AF: 0.267 AC: 2823 AN: 10554

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12635 AN: 67956

Other (OTH) AF: 0.252 AC: 531 AN: 2104

Alfa AF: 0.223 Hom.: 11928

Bravo AF: 0.284

Asia WGS AF: 0.370 AC: 1284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.73
PhyloP100		-0.050
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: rs3814058; hg19: chr3-119537291;