rs1464603

Variant names:

• chr3-119807502-G-A
• rs1464603
• ENST00000648112.1:c.*275G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-119807502-G-A
• chr3-119807502-G-C
• chr3-119807502-G-T

Variant summary

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

The ENST00000648112.1(ENSG00000285585):​c.*275G>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 0.634 in 1,484,310 control chromosomes in the GnomAD database, including 308,872 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 0.51 (23968 hom., cov: 33)
  • Exomes 𝑓: 0.65 (284904 hom.)
• Consequence: ENSG00000285585 ENST00000648112.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 17 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.66 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	NM_003889.4	MANE Select	c.197+55G>A		intron	N/A	NP_003880.3
	NR1I2	NM_022002.3		c.314+55G>A		intron	N/A	NP_071285.1	O75469-7
	NR1I2	NM_033013.3		c.197+55G>A		intron	N/A	NP_148934.1	O75469-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285585	ENST00000648112.1		c.*275G>A		3_prime_UTR	Exon 18 of 18	ENSP00000497876.1
	NR1I2	ENST00000393716.8	TSL:1 MANE Select	c.197+55G>A		intron	N/A	ENSP00000377319.3	O75469-1
	NR1I2	ENST00000337940.4	TSL:1	c.314+55G>A		intron	N/A	ENSP00000336528.4	O75469-7

Frequencies

GnomAD3 genomes AF: 0.513 AC: 78013 AN: 152040 Hom.: 23977 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.540

GnomAD4 exome AF: 0.648 AC: 863020 AN: 1332152 Hom.: 284904 AF XY: 0.647 AC XY: 433228 AN XY: 669344

African (AFR) AF: 0.130 AC: 4006 AN: 30764

American (AMR) AF: 0.703 AC: 31072 AN: 44218

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 17017 AN: 25334

East Asian (EAS) AF: 0.580 AC: 22681 AN: 39092

South Asian (SAS) AF: 0.582 AC: 48456 AN: 83234

European-Finnish (FIN) AF: 0.615 AC: 31540 AN: 51250

Middle Eastern (MID) AF: 0.600 AC: 2356 AN: 3928

European-Non Finnish (NFE) AF: 0.672 AC: 671209 AN: 998316

Other (OTH) AF: 0.619 AC: 34683 AN: 56016

GnomAD4 genome AF: 0.513 AC: 78006 AN: 152158 Hom.: 23968 Cov.: 33 AF XY: 0.517 AC XY: 38443 AN XY: 74390

African (AFR) AF: 0.151 AC: 6270 AN: 41524

American (AMR) AF: 0.647 AC: 9881 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2329 AN: 3472

East Asian (EAS) AF: 0.622 AC: 3211 AN: 5164

South Asian (SAS) AF: 0.569 AC: 2746 AN: 4824

European-Finnish (FIN) AF: 0.609 AC: 6441 AN: 10584

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.665 AC: 45201 AN: 67994

Other (OTH) AF: 0.540 AC: 1139 AN: 2108

Alfa AF: 0.595 Hom.: 54855

Bravo AF: 0.503

Asia WGS AF: 0.568 AC: 1977 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.24
DANN	Benign	0.66
PhyloP100		-0.032
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

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

Other links and lift over

dbSNP: rs1464603;

hg19: chr3-119526349;