rs6438550

Variant names:

• chr3-119817970-G-A
• rs6438550
• NM_003889.4:c.*758G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-119817970-G-A
• chr3-119817970-G-C

Variant summary

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

The NM_003889.4(NR1I2):​c.*758G>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 0.943 in 985,340 control chromosomes in the GnomAD database, including 438,608 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 0.92 (64795 hom., cov: 32)
  • Exomes 𝑓: 0.95 (373813 hom.)
• Consequence: NR1I2 NM_003889.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.*758G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.*758G>A		3_prime_UTR_variant	Exon 9 of 9		NP_071285.1
NR1I2	NM_033013.3	c.*758G>A		3_prime_UTR_variant	Exon 9 of 9		NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.*758G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_003889.4	ENSP00000377319.3
NR1I2	ENST00000337940.4	c.*758G>A		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000336528.4
NR1I2	ENST00000466380.6	c.*758G>A		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000420297.2
NR1I2	ENST00000493757.1	n.2195G>A		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes AF: 0.922 AC: 140228 AN: 152144 Hom.: 64744 Cov.: 32

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.954

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.948

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.925

GnomAD4 exome AF: 0.947 AC: 789039 AN: 833078 Hom.: 373813 Cov.: 26 AF XY: 0.948 AC XY: 364531 AN XY: 384720

African (AFR) AF: 0.849 AC: 13402 AN: 15784

American (AMR) AF: 0.971 AC: 955 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.951 AC: 4901 AN: 5154

East Asian (EAS) AF: 0.909 AC: 3300 AN: 3632

South Asian (SAS) AF: 0.874 AC: 14379 AN: 16460

European-Finnish (FIN) AF: 0.929 AC: 262 AN: 282

Middle Eastern (MID) AF: 0.937 AC: 1518 AN: 1620

European-Non Finnish (NFE) AF: 0.951 AC: 724853 AN: 761862

Other (OTH) AF: 0.933 AC: 25469 AN: 27300

GnomAD4 genome AF: 0.922 AC: 140340 AN: 152262 Hom.: 64795 Cov.: 32 AF XY: 0.921 AC XY: 68550 AN XY: 74442

African (AFR) AF: 0.865 AC: 35893 AN: 41512

American (AMR) AF: 0.954 AC: 14606 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 3318 AN: 3472

East Asian (EAS) AF: 0.914 AC: 4725 AN: 5170

South Asian (SAS) AF: 0.865 AC: 4176 AN: 4828

European-Finnish (FIN) AF: 0.948 AC: 10065 AN: 10612

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.947 AC: 64456 AN: 68036

Other (OTH) AF: 0.922 AC: 1950 AN: 2116

Alfa AF: 0.941 Hom.: 258161

Bravo AF: 0.922

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.55
PhyloP100		-0.21
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: rs6438550; hg19: chr3-119536817;