rs1523127

chr3-119782192-C-A

Variant summary

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

The NM_003889.4(NR1I2):c.-131C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 154,076 control chromosomes in the GnomAD database, including 21,543 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 0.49 (21320 hom., cov: 33)
  • Exomes 𝑓: 0.47 (223 hom.)
• Consequence: NR1I2 NM_003889.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.925

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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1I2	NM_003889.4	c.-131C>A		5_prime_UTR_variant	1/9	ENST00000393716.8
NR1I2	NM_033013.3	c.-131C>A		5_prime_UTR_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1I2	ENST00000393716.8	c.-131C>A		5_prime_UTR_variant	1/9	1	NM_003889.4	P2
NR1I2	ENST00000466380.6	c.-131C>A		5_prime_UTR_variant	1/9	1		A2
NR1I2	ENST00000474090.1	n.158C>A		non_coding_transcript_exon_variant	1/3	1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75052 AN: 152040 Hom.: 21318 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.514

GnomAD4 exome AF: 0.466 AC: 894 AN: 1918 Hom.: 223 Cov.: 0 AF XY: 0.489 AC XY: 488 AN XY: 998

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.417

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.621

Gnomad4 SAS exome AF: 0.466

Gnomad4 FIN exome AF: 0.417

Gnomad4 NFE exome AF: 0.483

Gnomad4 OTH exome AF: 0.533

GnomAD4 genome AF: 0.493 AC: 75072 AN: 152158 Hom.: 21320 Cov.: 33 AF XY: 0.500 AC XY: 37226 AN XY: 74382

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.518

Alfa AF: 0.589 Hom.: 53613

Bravo AF: 0.476

Asia WGS AF: 0.679 AC: 2362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	8.4
Dann	Benign	0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1523127; hg19: chr3-119501039;