rs3814055

Positions:

• chr3-119781188-C-T

Variant summary

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

The ENST00000466380.6(NR1I2):​c.-1135C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,196 control chromosomes in the GnomAD database, including 9,775 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 0.35 (9767 hom., cov: 33)
  • Exomes 𝑓: 0.36 (8 hom.)
• Consequence: NR1I2 ENST00000466380.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000466380.6	c.-1135C>T		5_prime_UTR_variant	1/9	1		ENSP00000420297	A2

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53532 AN: 151956 Hom.: 9764 Cov.: 33

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.361

GnomAD4 exome AF: 0.361 AC: 44 AN: 122 Hom.: 8 Cov.: 0 AF XY: 0.400 AC XY: 24 AN XY: 60

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.700

Gnomad4 EAS exome AF: 0.313

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.371

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.352 AC: 53560 AN: 152074 Hom.: 9767 Cov.: 33 AF XY: 0.350 AC XY: 26040 AN XY: 74308

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.359

Alfa AF: 0.383 Hom.: 23644

Bravo AF: 0.348

Asia WGS AF: 0.272 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3814055; hg19: chr3-119500035;