3-119807525-G-A

Variant names:

• chr3-119807525-G-A
• rs1464602
• ENST00000648112.1:c.*298G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000648112.1(ENSG00000285585):​c.*298G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,278,430 control chromosomes in the GnomAD database, including 268,371 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 0.56 (25871 hom., cov: 32)
  • Exomes 𝑓: 0.65 (242500 hom.)
• Consequence: ENSG00000285585 ENST00000648112.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• Publications: 12 publications found

Genes affected

ENSG00000285585 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000648112.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	NM_003889.4	MANE Select	c.197+78G>A		intron	N/A	NP_003880.3
	NR1I2	NM_022002.3		c.314+78G>A		intron	N/A	NP_071285.1
	NR1I2	NM_033013.3		c.197+78G>A		intron	N/A	NP_148934.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285585	ENST00000648112.1		c.*298G>A		3_prime_UTR	Exon 18 of 18	ENSP00000497876.1
	NR1I2	ENST00000393716.8	TSL:1 MANE Select	c.197+78G>A		intron	N/A	ENSP00000377319.3
	NR1I2	ENST00000337940.4	TSL:1	c.314+78G>A		intron	N/A	ENSP00000336528.4

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85429 AN: 151946 Hom.: 25879 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.579

GnomAD4 exome AF: 0.652 AC: 733890 AN: 1126366 Hom.: 242500 AF XY: 0.650 AC XY: 372868 AN XY: 573722

African (AFR) AF: 0.299 AC: 8049 AN: 26946

American (AMR) AF: 0.719 AC: 30237 AN: 42082

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 16216 AN: 23948

East Asian (EAS) AF: 0.585 AC: 22191 AN: 37920

South Asian (SAS) AF: 0.584 AC: 45401 AN: 77768

European-Finnish (FIN) AF: 0.616 AC: 28850 AN: 46872

Middle Eastern (MID) AF: 0.609 AC: 2141 AN: 3514

European-Non Finnish (NFE) AF: 0.672 AC: 549593 AN: 817924

Other (OTH) AF: 0.632 AC: 31212 AN: 49392

GnomAD4 genome AF: 0.562 AC: 85440 AN: 152064 Hom.: 25871 Cov.: 32 AF XY: 0.564 AC XY: 41899 AN XY: 74322

African (AFR) AF: 0.317 AC: 13130 AN: 41462

American (AMR) AF: 0.668 AC: 10219 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2344 AN: 3470

East Asian (EAS) AF: 0.636 AC: 3278 AN: 5156

South Asian (SAS) AF: 0.573 AC: 2758 AN: 4816

European-Finnish (FIN) AF: 0.609 AC: 6440 AN: 10576

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45256 AN: 67972

Other (OTH) AF: 0.579 AC: 1221 AN: 2110

Alfa AF: 0.562 Hom.: 11549

Bravo AF: 0.559

Asia WGS AF: 0.586 AC: 2040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.0
DANN	Benign	0.82
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1464602; hg19: chr3-119526372;