rs3814055

Variant names:

• chr3-119781188-C-T
• rs3814055
• ENST00000466380.6:c.-1135C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 132 publications found

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]

NR1I2 Gene-Disease associations (from GenCC):

• pediatric lymphoma

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000285585 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000466380.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	ENST00000466380.6	TSL:1	c.-1135C>T		5_prime_UTR	Exon 1 of 9	ENSP00000420297.2	O75469-4
	ENSG00000285585	ENST00000648112.1		c.*2-26041C>T		intron	N/A	ENSP00000497876.1

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.500 AC: 2 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 7 AN: 10

East Asian (EAS) AF: 0.313 AC: 5 AN: 16

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.286 AC: 4 AN: 14

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.371 AC: 26 AN: 70

Other (OTH) AF: 0.00 AC: 0 AN: 6

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

African (AFR) AF: 0.287 AC: 11920 AN: 41510

American (AMR) AF: 0.367 AC: 5618 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1731 AN: 3472

East Asian (EAS) AF: 0.222 AC: 1149 AN: 5172

South Asian (SAS) AF: 0.371 AC: 1788 AN: 4820

European-Finnish (FIN) AF: 0.365 AC: 3853 AN: 10548

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26197 AN: 67942

Other (OTH) AF: 0.359 AC: 759 AN: 2114

Alfa AF: 0.376 Hom.: 49689

Bravo AF: 0.348

Asia WGS AF: 0.272 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.72
PhyloP100		-1.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3814055;

hg19: chr3-119500035;