3-119787615-T-C

Variant names:

• chr3-119787615-T-C
• rs2056530
• NM_003889.4:c.-23+5315T>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.-23+5315T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 150,912 control chromosomes in the GnomAD database, including 41,960 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 0.72 (41960 hom., cov: 27)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119
• Publications: 7 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

ENSG00000285585 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.-23+5315T>C		intron	N/A	NP_003880.3
	NR1I2	NM_022002.3		c.95+4763T>C		intron	N/A	NP_071285.1
	NR1I2	NM_033013.3		c.-23+5315T>C		intron	N/A	NP_148934.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	ENST00000393716.8	TSL:1 MANE Select	c.-23+5315T>C		intron	N/A	ENSP00000377319.3
	ENSG00000285585	ENST00000648112.1		c.*2-19614T>C		intron	N/A	ENSP00000497876.1
	NR1I2	ENST00000337940.4	TSL:1	c.95+4763T>C		intron	N/A	ENSP00000336528.4

Frequencies

GnomAD3 genomes AF: 0.722 AC: 108868 AN: 150794 Hom.: 41947 Cov.: 27

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.834

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.871

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.755

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.722 AC: 108910 AN: 150912 Hom.: 41960 Cov.: 27 AF XY: 0.731 AC XY: 53831 AN XY: 73610

African (AFR) AF: 0.428 AC: 17523 AN: 40918

American (AMR) AF: 0.834 AC: 12667 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2728 AN: 3462

East Asian (EAS) AF: 0.999 AC: 5130 AN: 5136

South Asian (SAS) AF: 0.844 AC: 4005 AN: 4744

European-Finnish (FIN) AF: 0.871 AC: 8991 AN: 10318

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55264 AN: 67852

Other (OTH) AF: 0.758 AC: 1591 AN: 2098

Alfa AF: 0.785 Hom.: 69944

Bravo AF: 0.706

Asia WGS AF: 0.896 AC: 3110 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.1
DANN	Benign	0.68
PhyloP100		0.12
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: rs2056530; hg19: chr3-119506462;