rs2276706

Positions:

• chr3-119782460-G-A

Variant summary

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

The NM_003889.4(NR1I2):​c.-23+160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 148,734 control chromosomes in the GnomAD database, including 9,439 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 0.35 (9439 hom., cov: 29)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1I2	NM_003889.4	c.-23+160G>A		intron_variant		ENST00000393716.8
NR1I2	NM_033013.3	c.-23+160G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1I2	ENST00000393716.8	c.-23+160G>A		intron_variant		1	NM_003889.4	P2
NR1I2	ENST00000466380.6	c.-23+160G>A		intron_variant		1		A2
NR1I2	ENST00000474090.1	n.266+160G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 52622 AN: 148640 Hom.: 9439 Cov.: 29

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.354 AC: 52640 AN: 148734 Hom.: 9439 Cov.: 29 AF XY: 0.352 AC XY: 25500 AN XY: 72414

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.361

Alfa AF: 0.383 Hom.: 2616

Bravo AF: 0.348

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.3
DANN	Benign	0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2276706; hg19: chr3-119501307;