NM_003889.4:c.*1195A>C

Variant names:

• chr3-119818407-A-C
• rs3814057
• NM_003889.4:c.*1195A>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.*1195A>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 984,094 control chromosomes in the GnomAD database, including 22,026 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 (7119 hom., cov: 32)
  • Exomes 𝑓: 0.18 (14907 hom.)
• Consequence: NR1I2 NM_003889.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575
• Publications: 44 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 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.*1195A>C		3_prime_UTR	Exon 9 of 9	NP_003880.3
	NR1I2	NM_022002.3		c.*1195A>C		3_prime_UTR	Exon 9 of 9	NP_071285.1	O75469-7
	NR1I2	NM_033013.3		c.*1195A>C		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.*1195A>C		3_prime_UTR	Exon 9 of 9	ENSP00000377319.3	O75469-1
	NR1I2	ENST00000337940.4	TSL:1	c.*1195A>C		3_prime_UTR	Exon 9 of 9	ENSP00000336528.4	O75469-7
	NR1I2	ENST00000466380.6	TSL:1	c.*1195A>C		3_prime_UTR	Exon 9 of 9	ENSP00000420297.2	O75469-4

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42546 AN: 151884 Hom.: 7103 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.484

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: 150898 AN: 832092 Hom.: 14907 Cov.: 25 AF XY: 0.181 AC XY: 69618 AN XY: 384306

African (AFR) AF: 0.471 AC: 7416 AN: 15756

American (AMR) AF: 0.198 AC: 194 AN: 978

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 1002 AN: 5142

East Asian (EAS) AF: 0.486 AC: 1761 AN: 3624

South Asian (SAS) AF: 0.279 AC: 4577 AN: 16430

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

Middle Eastern (MID) AF: 0.239 AC: 385 AN: 1614

European-Non Finnish (NFE) AF: 0.170 AC: 129594 AN: 761022

Other (OTH) AF: 0.217 AC: 5907 AN: 27250

GnomAD4 genome AF: 0.280 AC: 42610 AN: 152002 Hom.: 7119 Cov.: 32 AF XY: 0.282 AC XY: 20974 AN XY: 74320

African (AFR) AF: 0.448 AC: 18556 AN: 41404

American (AMR) AF: 0.219 AC: 3356 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3468

East Asian (EAS) AF: 0.484 AC: 2499 AN: 5158

South Asian (SAS) AF: 0.291 AC: 1405 AN: 4822

European-Finnish (FIN) AF: 0.267 AC: 2814 AN: 10552

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

European-Non Finnish (NFE) AF: 0.186 AC: 12639 AN: 67992

Other (OTH) AF: 0.252 AC: 531 AN: 2108

Alfa AF: 0.215 Hom.: 15370

Bravo AF: 0.284

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.3
DANN	Benign	0.85
PhyloP100		0.57
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: rs3814057; hg19: chr3-119537254;