rs12721615

chr3-119818376-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003889.4(NR1I2):c.*1164A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00978 in 985,372 control chromosomes in the GnomAD database, including 58 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 0.0055 (6 hom., cov: 32)
  • Exomes 𝑓: 0.011 (52 hom.)
• Consequence: NR1I2 NM_003889.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1I2	NM_003889.4	c.*1164A>G		3_prime_UTR_variant	9/9	ENST00000393716.8
NR1I2	NM_022002.3	c.*1164A>G		3_prime_UTR_variant	9/9
NR1I2	NM_033013.3	c.*1164A>G		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1I2	ENST00000393716.8	c.*1164A>G		3_prime_UTR_variant	9/9	1	NM_003889.4	P2
NR1I2	ENST00000337940.4	c.*1164A>G		3_prime_UTR_variant	9/9	1		A2
NR1I2	ENST00000466380.6	c.*1164A>G		3_prime_UTR_variant	9/9	1		A2
NR1I2	ENST00000493757.1	n.2601A>G		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.00553 AC: 841 AN: 152214 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.00471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.000960

GnomAD4 exome AF: 0.0106 AC: 8794 AN: 833040 Hom.: 52 Cov.: 32 AF XY: 0.0106 AC XY: 4068 AN XY: 384682

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.00204

Gnomad4 ASJ exome AF: 0.000582

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00152

Gnomad4 FIN exome AF: 0.0109

Gnomad4 NFE exome AF: 0.0112

Gnomad4 OTH exome AF: 0.00784

GnomAD4 genome AF: 0.00552 AC: 841 AN: 152332 Hom.: 6 Cov.: 32 AF XY: 0.00516 AC XY: 384 AN XY: 74490

Gnomad4 AFR AF: 0.00173

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00165

Gnomad4 FIN AF: 0.00471

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.000950

Alfa AF: 0.00872 Hom.: 8

Bravo AF: 0.00549

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	5.6
Dann	Benign	0.90

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: rs12721615; hg19: chr3-119537223;