rs2461825

Variant names:

• chr3-119810758-A-G
• rs2461825
• NM_003889.4:c.331+564A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-119810758-A-G
• chr3-119810758-A-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.331+564A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 152,116 control chromosomes in the GnomAD database, including 26,229 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 0.54 (26229 hom., cov: 32)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 10 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.331+564A>G		intron_variant	Intron 3 of 8	ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.448+564A>G		intron_variant	Intron 3 of 8		NP_071285.1
NR1I2	NM_033013.3	c.331+564A>G		intron_variant	Intron 3 of 8		NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.331+564A>G		intron_variant	Intron 3 of 8	1	NM_003889.4	ENSP00000377319.3
NR1I2	ENST00000337940.4	c.448+564A>G		intron_variant	Intron 3 of 8	1		ENSP00000336528.4
NR1I2	ENST00000466380.6	c.331+564A>G		intron_variant	Intron 3 of 8	1		ENSP00000420297.2
NR1I2	ENST00000474090.1	n.*206A>G		downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81574 AN: 151998 Hom.: 26243 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.536 AC: 81562 AN: 152116 Hom.: 26229 Cov.: 32 AF XY: 0.540 AC XY: 40133 AN XY: 74356

African (AFR) AF: 0.156 AC: 6468 AN: 41518

American (AMR) AF: 0.664 AC: 10155 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2391 AN: 3468

East Asian (EAS) AF: 0.664 AC: 3423 AN: 5158

South Asian (SAS) AF: 0.584 AC: 2813 AN: 4814

European-Finnish (FIN) AF: 0.642 AC: 6801 AN: 10586

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.698 AC: 47434 AN: 67972

Other (OTH) AF: 0.563 AC: 1187 AN: 2110

Alfa AF: 0.582 Hom.: 6330

Bravo AF: 0.525

Asia WGS AF: 0.592 AC: 2061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.54
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2461825; hg19: chr3-119529605;