rs6785049

Variant names:

• chr3-119814886-G-A
• rs6785049
• NM_003889.4:c.795-93G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-119814886-G-A
• chr3-119814886-G-T

Variant summary

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

The NM_003889.4(NR1I2):​c.795-93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,522,460 control chromosomes in the GnomAD database, including 264,234 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 0.46 (19763 hom., cov: 32)
  • Exomes 𝑓: 0.59 (244471 hom.)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.58
• Publications: 109 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 (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

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.795-93G>A		intron	N/A	NP_003880.3
	NR1I2	NM_022002.3		c.912-93G>A		intron	N/A	NP_071285.1	O75469-7
	NR1I2	NM_033013.3		c.684-93G>A		intron	N/A	NP_148934.1	O75469-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	ENST00000393716.8	TSL:1 MANE Select	c.795-93G>A		intron	N/A	ENSP00000377319.3	O75469-1
	NR1I2	ENST00000337940.4	TSL:1	c.912-93G>A		intron	N/A	ENSP00000336528.4	O75469-7
	NR1I2	ENST00000466380.6	TSL:1	c.684-93G>A		intron	N/A	ENSP00000420297.2	O75469-4

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70065 AN: 151908 Hom.: 19765 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.480

GnomAD4 exome AF: 0.590 AC: 808743 AN: 1370434 Hom.: 244471 AF XY: 0.589 AC XY: 403256 AN XY: 685206

African (AFR) AF: 0.0978 AC: 3085 AN: 31550

American (AMR) AF: 0.656 AC: 28199 AN: 42960

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 15311 AN: 25424

East Asian (EAS) AF: 0.430 AC: 16744 AN: 38970

South Asian (SAS) AF: 0.520 AC: 43202 AN: 83122

European-Finnish (FIN) AF: 0.608 AC: 28663 AN: 47124

Middle Eastern (MID) AF: 0.540 AC: 2319 AN: 4292

European-Non Finnish (NFE) AF: 0.615 AC: 639479 AN: 1039654

Other (OTH) AF: 0.554 AC: 31741 AN: 57338

GnomAD4 genome AF: 0.461 AC: 70061 AN: 152026 Hom.: 19763 Cov.: 32 AF XY: 0.464 AC XY: 34474 AN XY: 74302

African (AFR) AF: 0.120 AC: 4956 AN: 41464

American (AMR) AF: 0.578 AC: 8841 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2116 AN: 3472

East Asian (EAS) AF: 0.414 AC: 2138 AN: 5166

South Asian (SAS) AF: 0.505 AC: 2430 AN: 4808

European-Finnish (FIN) AF: 0.613 AC: 6489 AN: 10588

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41324 AN: 67922

Other (OTH) AF: 0.479 AC: 1010 AN: 2108

Alfa AF: 0.573 Hom.: 75768

Bravo AF: 0.446

Asia WGS AF: 0.428 AC: 1493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0080
DANN	Benign	0.54
PhyloP100		-4.6
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: rs6785049; hg19: chr3-119533733;