3-119818444-T-C

Position:

• chr3-119818444-T-C

Variant summary

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

The NM_003889.4(NR1I2):​c.*1232T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 983,836 control chromosomes in the GnomAD database, including 22,029 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 0.28 (7128 hom., cov: 32)
  • Exomes 𝑓: 0.18 (14901 hom.)
• Consequence: NR1I2 NM_003889.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.*1232T>C		3_prime_UTR_variant	9/9	ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.*1232T>C		3_prime_UTR_variant	9/9		NP_071285.1
NR1I2	NM_033013.3	c.*1232T>C		3_prime_UTR_variant	9/9		NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.*1232T>C		3_prime_UTR_variant	9/9	1	NM_003889.4	ENSP00000377319	P2
NR1I2	ENST00000337940.4	c.*1232T>C		3_prime_UTR_variant	9/9	1		ENSP00000336528	A2
NR1I2	ENST00000466380.6	c.*1232T>C		3_prime_UTR_variant	9/9	1		ENSP00000420297	A2
NR1I2	ENST00000493757.1	n.2669T>C		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42556 AN: 151804 Hom.: 7112 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.253

GnomAD4 exome AF: 0.181 AC: 150757 AN: 831914 Hom.: 14901 Cov.: 29 AF XY: 0.181 AC XY: 69528 AN XY: 384176

Gnomad4 AFR exome AF: 0.471

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.195

Gnomad4 EAS exome AF: 0.486

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.225

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.217

GnomAD4 genome AF: 0.281 AC: 42620 AN: 151922 Hom.: 7128 Cov.: 32 AF XY: 0.282 AC XY: 20967 AN XY: 74260

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.252

Alfa AF: 0.212 Hom.: 4014

Bravo AF: 0.284

Asia WGS AF: 0.370 AC: 1284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.73

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: rs3814058; hg19: chr3-119537291;