chr3-119781817-A-G

Position:

• chr3-119781817-A-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/exons	MANE	Protein	UniProt
		n.119781817A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000466380	c.-506A>G		5_prime_UTR_variant	1/9	1		ENSP00000420297.2
ENSG00000285585	ENST00000648112.1	c.*2-25412A>G		intron_variant				ENSP00000497876.1

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;