3-119807525-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000648112.1(ENSG00000285585):​c.*298G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000285585 ENST00000648112.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

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>C		intron	N/A	NP_003880.3
	NR1I2	NM_022002.3		c.314+78G>C		intron	N/A	NP_071285.1
	NR1I2	NM_033013.3		c.197+78G>C		intron	N/A	NP_148934.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1128694 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 574854

African (AFR) AF: 0.00 AC: 0 AN: 27004

American (AMR) AF: 0.00 AC: 0 AN: 42114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23964

East Asian (EAS) AF: 0.00 AC: 0 AN: 37938

South Asian (SAS) AF: 0.00 AC: 0 AN: 77838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3520

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 819918

Other (OTH) AF: 0.00 AC: 0 AN: 49466

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.2
DANN	Benign	0.80
PhyloP100		-0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;