chr3-119816948-C-G

Variant names:

• chr3-119816948-C-G
• rs11929668
• NM_003889.4:c.1161-120C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003889.4(NR1I2):​c.1161-120C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,327,874 control chromosomes in the GnomAD database, including 14,338 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 (1508 hom., cov: 32)
  • Exomes 𝑓: 0.14 (12830 hom.)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.741
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.1161-120C>G		intron_variant	Intron 8 of 8	ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.1278-120C>G		intron_variant	Intron 8 of 8		NP_071285.1
NR1I2	NM_033013.3	c.1050-120C>G		intron_variant	Intron 8 of 8		NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.1161-120C>G		intron_variant	Intron 8 of 8	1	NM_003889.4	ENSP00000377319.3
NR1I2	ENST00000337940.4	c.1278-120C>G		intron_variant	Intron 8 of 8	1		ENSP00000336528.4
NR1I2	ENST00000466380.6	c.1050-120C>G		intron_variant	Intron 8 of 8	1		ENSP00000420297.2
NR1I2	ENST00000493757.1	n.1293-120C>G		intron_variant	Intron 5 of 5	2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20410 AN: 152000 Hom.: 1508 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0623

Gnomad FIN AF: 0.0604

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.140 AC: 164509 AN: 1175756 Hom.: 12830 AF XY: 0.137 AC XY: 81985 AN XY: 596544

African (AFR) AF: 0.146 AC: 4046 AN: 27770

American (AMR) AF: 0.0894 AC: 3688 AN: 41236

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 3735 AN: 23996

East Asian (EAS) AF: 0.000267 AC: 10 AN: 37424

South Asian (SAS) AF: 0.0672 AC: 5239 AN: 77952

European-Finnish (FIN) AF: 0.0778 AC: 3653 AN: 46978

Middle Eastern (MID) AF: 0.144 AC: 756 AN: 5234

European-Non Finnish (NFE) AF: 0.158 AC: 136335 AN: 864360

Other (OTH) AF: 0.139 AC: 7047 AN: 50806

GnomAD4 genome AF: 0.134 AC: 20415 AN: 152118 Hom.: 1508 Cov.: 32 AF XY: 0.129 AC XY: 9590 AN XY: 74374

African (AFR) AF: 0.143 AC: 5954 AN: 41494

American (AMR) AF: 0.140 AC: 2141 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 536 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5178

South Asian (SAS) AF: 0.0617 AC: 297 AN: 4814

European-Finnish (FIN) AF: 0.0604 AC: 640 AN: 10594

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

European-Non Finnish (NFE) AF: 0.151 AC: 10268 AN: 67974

Other (OTH) AF: 0.157 AC: 331 AN: 2108

Alfa AF: 0.139 Hom.: 220

Bravo AF: 0.140

Asia WGS AF: 0.0370 AC: 130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.50
PhyloP100		-0.74
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: rs11929668; hg19: chr3-119535795;