3-119817734-C-T

Variant names:

• chr3-119817734-C-T
• rs3732360
• NM_003889.4:c.*522C>T

Variant summary

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

The NM_003889.4(NR1I2):​c.*522C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 1,028,112 control chromosomes in the GnomAD database, including 265,513 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 0.61 (30214 hom., cov: 32)
  • Exomes 𝑓: 0.73 (235299 hom.)
• Consequence: NR1I2 NM_003889.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.*522C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.*522C>T		3_prime_UTR_variant	Exon 9 of 9		NP_071285.1
NR1I2	NM_033013.3	c.*522C>T		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.*522C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_003889.4	ENSP00000377319.3
NR1I2	ENST00000337940.4	c.*522C>T		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000336528.4
NR1I2	ENST00000466380.6	c.*522C>T		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000420297.2
NR1I2	ENST00000493757.1	n.1959C>T		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92355 AN: 151942 Hom.: 30210 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.636

GnomAD4 exome AF: 0.729 AC: 638654 AN: 876052 Hom.: 235299 Cov.: 37 AF XY: 0.729 AC XY: 296541 AN XY: 406662

Gnomad4 AFR exome AF: 0.329

Gnomad4 AMR exome AF: 0.731

Gnomad4 ASJ exome AF: 0.744

Gnomad4 EAS exome AF: 0.434

Gnomad4 SAS exome AF: 0.572

Gnomad4 FIN exome AF: 0.661

Gnomad4 NFE exome AF: 0.747

Gnomad4 OTH exome AF: 0.684

GnomAD4 genome AF: 0.608 AC: 92394 AN: 152060 Hom.: 30214 Cov.: 32 AF XY: 0.605 AC XY: 44992 AN XY: 74320

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.747

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.731

Gnomad4 OTH AF: 0.634

Alfa AF: 0.713 Hom.: 77560

Bravo AF: 0.603

Asia WGS AF: 0.484 AC: 1687 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	0.27
DANN	Benign	0.72

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: rs3732360; hg19: chr3-119536581;