3-119780660-T-C

Variant summary

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

The ENST00000466380.6(NR1I2):c.-1663T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 152,208 control chromosomes in the GnomAD database, including 20,652 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 0.48 (20647 hom., cov: 33)
  • Exomes 𝑓: 0.42 (5 hom.)
• Consequence: NR1I2 ENST00000466380.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475

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 (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1I2	ENST00000466380.6	c.-1663T>C		5_prime_UTR_variant	1/9	1		A2

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72807 AN: 152040 Hom.: 20640 Cov.: 33

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.493

GnomAD4 exome AF: 0.417 AC: 20 AN: 48 Hom.: 5 Cov.: 0 AF XY: 0.471 AC XY: 16 AN XY: 34

Gnomad4 AMR exome AF: 0.750

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.368

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.479 AC: 72831 AN: 152160 Hom.: 20647 Cov.: 33 AF XY: 0.486 AC XY: 36113 AN XY: 74374

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.497

Alfa AF: 0.582 Hom.: 53068

Bravo AF: 0.460

Asia WGS AF: 0.657 AC: 2283 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	4.2
Dann	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1523130; hg19: chr3-119499507;