rs2472682

Positions:

• chr3-119813805-A-C
• chr3-119813805-A-G
• chr3-119813805-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003889.4(NR1I2):​c.794+845A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,974 control chromosomes in the GnomAD database, including 22,582 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 0.51 (22582 hom., cov: 31)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1I2	NM_003889.4	c.794+845A>C		intron_variant		ENST00000393716.8
NR1I2	NM_022002.3	c.911+845A>C		intron_variant
NR1I2	NM_033013.3	c.683+845A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1I2	ENST00000393716.8	c.794+845A>C		intron_variant		1	NM_003889.4	P2
NR1I2	ENST00000337940.4	c.911+845A>C		intron_variant		1		A2
NR1I2	ENST00000466380.6	c.683+845A>C		intron_variant		1		A2
NR1I2	ENST00000493757.1	n.926+845A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77880 AN: 151856 Hom.: 22583 Cov.: 31

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.513 AC: 77890 AN: 151974 Hom.: 22582 Cov.: 31 AF XY: 0.513 AC XY: 38119 AN XY: 74278

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.533

Alfa AF: 0.615 Hom.: 38413

Bravo AF: 0.500

Asia WGS AF: 0.457 AC: 1593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs2472682; hg19: chr3-119532652;