3-119817728-G-T

Variant names:

• chr3-119817728-G-T
• rs56147004
• NM_003889.4:c.*516G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003889.4(NR1I2):​c.*516G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00676 in 1,045,946 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.0040 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0072 (26 hom.)
• Consequence: NR1I2 NM_003889.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643
• Publications: 1 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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS2: High Homozygotes in GnomAdExome4 at 26 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003889.4. 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
	NR1I2	NM_003889.4	MANE Select	c.*516G>T		3_prime_UTR	Exon 9 of 9	NP_003880.3
	NR1I2	NM_022002.3		c.*516G>T		3_prime_UTR	Exon 9 of 9	NP_071285.1
	NR1I2	NM_033013.3		c.*516G>T		3_prime_UTR	Exon 9 of 9	NP_148934.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	ENST00000393716.8	TSL:1 MANE Select	c.*516G>T		3_prime_UTR	Exon 9 of 9	ENSP00000377319.3
	NR1I2	ENST00000337940.4	TSL:1	c.*516G>T		3_prime_UTR	Exon 9 of 9	ENSP00000336528.4
	NR1I2	ENST00000466380.6	TSL:1	c.*516G>T		3_prime_UTR	Exon 9 of 9	ENSP00000420297.2

Frequencies

GnomAD3 genomes AF: 0.00396 AC: 603 AN: 152108 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00689

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.00724 AC: 6467 AN: 893720 Hom.: 26 Cov.: 37 AF XY: 0.00721 AC XY: 2998 AN XY: 415820

African (AFR) AF: 0.000709 AC: 13 AN: 18336

American (AMR) AF: 0.00203 AC: 10 AN: 4936

Ashkenazi Jewish (ASJ) AF: 0.00680 AC: 45 AN: 6616

East Asian (EAS) AF: 0.00 AC: 0 AN: 7598

South Asian (SAS) AF: 0.000339 AC: 8 AN: 23566

European-Finnish (FIN) AF: 0.00123 AC: 3 AN: 2434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1872

European-Non Finnish (NFE) AF: 0.00771 AC: 6153 AN: 797928

Other (OTH) AF: 0.00772 AC: 235 AN: 30434

GnomAD4 genome AF: 0.00396 AC: 603 AN: 152226 Hom.: 1 Cov.: 33 AF XY: 0.00359 AC XY: 267 AN XY: 74424

African (AFR) AF: 0.00159 AC: 66 AN: 41530

American (AMR) AF: 0.00124 AC: 19 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00689 AC: 469 AN: 68024

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00213 Hom.: 1

Bravo AF: 0.00397

Asia WGS AF: 0.000289 AC: 1 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	0.57
DANN	Benign	0.78
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism

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: rs56147004; hg19: chr3-119536575;