3-119781817-A-G

Variant names:

• chr3-119781817-A-G
• rs1523128
• ENST00000466380:c.-506A>G

Variant summary

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

The ENST00000466380(NR1I2):​c.-506A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 152,206 control chromosomes in the GnomAD database, including 63,304 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 0.90 (63300 hom., cov: 32)
  • Exomes 𝑓: 1.0 (4 hom.)
• Consequence: NR1I2 ENST00000466380 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372

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]

ENSG00000285585 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000466380	c.-506A>G		5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000420297.2
ENSG00000285585	ENST00000648112.1	c.*2-25412A>G		intron_variant	Intron 17 of 17			ENSP00000497876.1
NR1I2	ENST00000474090.1	n.-218A>G		upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.901 AC: 136996 AN: 152080 Hom.: 63281 Cov.: 32

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.968

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.994

Gnomad OTH AF: 0.921

GnomAD4 exome AF: 1.00 AC: 8 AN: 8 Hom.: 4 Cov.: 0 AF XY: 1.00 AC XY: 8 AN XY: 8

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.901 AC: 137071 AN: 152198 Hom.: 63300 Cov.: 32 AF XY: 0.905 AC XY: 67352 AN XY: 74428

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.961

Gnomad4 ASJ AF: 0.997

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.968

Gnomad4 FIN AF: 0.997

Gnomad4 NFE AF: 0.994

Gnomad4 OTH AF: 0.922

Alfa AF: 0.980 Hom.: 107088

Bravo AF: 0.886

Asia WGS AF: 0.965 AC: 3358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1523128; hg19: chr3-119500664;