Genetic Variant NR1I2:c.-506A>G (chr3-119781817-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000466380.6(NR1I2):c.-506A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 152,206 control chromosomes in the GnomAD database, including 63,304 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 0.90 ( 63300 hom., cov: 32)

Exomes 𝑓: 1.0 ( 4 hom. )

Consequence

NR1I2
ENST00000466380.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.372

Publications

9 publications found

Variant links:

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

NR1I2 links:

ENSG00000285585 (HGNC:):

ENSG00000285585 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000466380.6. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NR1I2	ENST00000466380.6	TSL:1	c.-506A>G	5_prime_UTR	Exon 1 of 9	ENSP00000420297.2	O75469-4
ENSG00000285585	ENST00000648112.1		c.*2-25412A>G	intron	N/A	ENSP00000497876.1
NR1I2	ENST00000474090.1	TSL:1	n.-218A>G	upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.901

AC:

136996

AN:

152080

Hom.:

63281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.669

Gnomad AMI

AF:

0.987

Gnomad AMR

AF:

0.961

Gnomad ASJ

AF:

0.997

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.968

Gnomad FIN

AF:

0.997

Gnomad MID

AF:

0.978

Gnomad NFE

AF:

0.994

Gnomad OTH

AF:

0.921

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.901

AC:

137071

AN:

152198

Hom.:

63300

Cov.:

AF XY:

0.905

AC XY:

67352

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.669

AC:

27737

AN:

41454

American (AMR)

AF:

0.961

AC:

14701

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.997

AC:

3460

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5179

AN:

5180

South Asian (SAS)

AF:

0.968

AC:

4670

AN:

4826

European-Finnish (FIN)

AF:

0.997

AC:

10583

AN:

10620

Middle Eastern (MID)

AF:

0.976

AC:

287

AN:

294

European-Non Finnish (NFE)

AF:

0.994

AC:

67609

AN:

68034

Other (OTH)

AF:

0.922

AC:

1947

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

520

1041

1561

2082

2602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.954

Hom.:

162627

Bravo

AF:

0.886

Asia WGS

AF:

0.965

AC:

3358

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

1.8

(source)

DANN

Benign

0.40

PhyloP100

-0.37

PromoterAI

0.011

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over