rs3732359

Variant names:

• chr3-119817582-G-A
• rs3732359
• NM_003889.4:c.*370G>A

Variant summary

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

The NM_003889.4(NR1I2):​c.*370G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 1,172,542 control chromosomes in the GnomAD database, including 325,041 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 0.63 (32448 hom., cov: 33)
  • Exomes 𝑓: 0.75 (292593 hom.)
• Consequence: NR1I2 NM_003889.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.*370G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.*370G>A		3_prime_UTR_variant	Exon 9 of 9		NP_071285.1
NR1I2	NM_033013.3	c.*370G>A		3_prime_UTR_variant	Exon 9 of 9		NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.*370G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_003889.4	ENSP00000377319.3
NR1I2	ENST00000337940.4	c.*370G>A		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000336528.4
NR1I2	ENST00000466380.6	c.*370G>A		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000420297.2
NR1I2	ENST00000493757.1	n.1807G>A		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95511 AN: 152032 Hom.: 32443 Cov.: 33

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.660

GnomAD4 exome AF: 0.752 AC: 767533 AN: 1020392 Hom.: 292593 Cov.: 46 AF XY: 0.749 AC XY: 362620 AN XY: 484236

Gnomad4 AFR exome AF: 0.345

Gnomad4 AMR exome AF: 0.751

Gnomad4 ASJ exome AF: 0.759

Gnomad4 EAS exome AF: 0.431

Gnomad4 SAS exome AF: 0.590

Gnomad4 FIN exome AF: 0.692

Gnomad4 NFE exome AF: 0.779

Gnomad4 OTH exome AF: 0.709

GnomAD4 genome AF: 0.628 AC: 95549 AN: 152150 Hom.: 32448 Cov.: 33 AF XY: 0.625 AC XY: 46514 AN XY: 74394

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.765

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.761

Gnomad4 OTH AF: 0.658

Alfa AF: 0.738 Hom.: 70739

Bravo AF: 0.623

Asia WGS AF: 0.494 AC: 1722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.80

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: rs3732359; hg19: chr3-119536429;