dbSNP rs2461817: NR1I2:c.-22-1425A>C (chr3-119805804-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003889.4(NR1I2):c.-22-1425A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 150,808 control chromosomes in the GnomAD database, including 23,668 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 0.55 ( 23668 hom., cov: 27)

Consequence

NR1I2
NM_003889.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.542

Publications

13 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:

Genome browser will be placed here

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=-0.75).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NR1I2	NM_003889.4 link	c.-22-1425A>C	intron_variant	Intron 1 of 8	ENST00000393716.8	NP_003880.3	O75469-1
NR1I2	NM_022002.3 link	c.96-1425A>C	intron_variant	Intron 1 of 8		NP_071285.1	O75469-7F1D8P9
NR1I2	NM_033013.3 link	c.-22-1425A>C	intron_variant	Intron 1 of 8		NP_148934.1	O75469-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8 link	c.-22-1425A>C		intron_variant	Intron 1 of 8	1	NM_003889.4	ENSP00000377319.3		O75469-1J3KPQ3
ENSG00000285585	ENST00000648112.1 link	c.*2-1425A>C		intron_variant	Intron 17 of 17			ENSP00000497876.1

Frequencies

GnomAD3 genomes

AF:

0.552

AC:

83214

AN:

150690

Hom.:

23660

Cov.:

show subpopulations

Gnomad AFR

AF:

0.417

Gnomad AMI

AF:

0.685

Gnomad AMR

AF:

0.533

Gnomad ASJ

AF:

0.640

Gnomad EAS

AF:

0.634

Gnomad SAS

AF:

0.562

Gnomad FIN

AF:

0.689

Gnomad MID

AF:

0.596

Gnomad NFE

AF:

0.605

Gnomad OTH

AF:

0.536

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.552

AC:

83264

AN:

150808

Hom.:

23668

Cov.:

AF XY:

0.558

AC XY:

41077

AN XY:

73558

show subpopulations

African (AFR)

AF:

0.417

AC:

17092

AN:

41018

American (AMR)

AF:

0.534

AC:

8056

AN:

15094

Ashkenazi Jewish (ASJ)

AF:

0.640

AC:

2214

AN:

3460

East Asian (EAS)

AF:

0.633

AC:

3236

AN:

5112

South Asian (SAS)

AF:

0.562

AC:

2685

AN:

4778

European-Finnish (FIN)

AF:

0.689

AC:

7053

AN:

10240

Middle Eastern (MID)

AF:

0.595

AC:

175

AN:

294

European-Non Finnish (NFE)

AF:

0.605

AC:

41011

AN:

67826

Other (OTH)

AF:

0.539

AC:

1123

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1762

3523

5285

7046

8808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

714

1428

2142

2856

3570

<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:

0.570

Hom.:

39967

Bravo

AF:

0.534

Asia WGS

AF:

0.576

AC:

2004

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

0.54

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over