dbSNP rs2276706: NR1I2:c.-23+160G>A (chr3-119782460-G-A) – 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.-23+160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 148,734 control chromosomes in the GnomAD database, including 9,439 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 0.35 ( 9439 hom., cov: 29)

Consequence

NR1I2
NM_003889.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.11

Publications

22 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=-0.76).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
NR1I2	NM_003889.4 link	c.-23+160G>A	intron_variant	Intron 1 of 8	ENST00000393716.8	NP_003880.3
NR1I2	NM_033013.3 link	c.-23+160G>A	intron_variant	Intron 1 of 8		NP_148934.1
NR1I2	NM_022002.3 link	c.-298G>A	upstream_gene_variant			NP_071285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8 link	c.-23+160G>A		intron_variant	Intron 1 of 8	1	NM_003889.4	ENSP00000377319.3
ENSG00000285585	ENST00000648112.1 link	c.*2-24769G>A		intron_variant	Intron 17 of 17			ENSP00000497876.1

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

52622

AN:

148640

Hom.:

9439

Cov.:

show subpopulations

Gnomad AFR

AF:

0.288

Gnomad AMI

AF:

0.456

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.224

Gnomad SAS

AF:

0.374

Gnomad FIN

AF:

0.367

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.363

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

GnomAD4 genome

AF:

0.354

AC:

52640

AN:

148734

Hom.:

9439

Cov.:

AF XY:

0.352

AC XY:

25500

AN XY:

72414

show subpopulations

African (AFR)

AF:

0.288

AC:

11589

AN:

40282

American (AMR)

AF:

0.371

AC:

5575

AN:

15034

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

1721

AN:

3444

East Asian (EAS)

AF:

0.224

AC:

1137

AN:

5080

South Asian (SAS)

AF:

0.373

AC:

1753

AN:

4698

European-Finnish (FIN)

AF:

0.367

AC:

3613

AN:

9836

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.387

AC:

25961

AN:

67088

Other (OTH)

AF:

0.361

AC:

748

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

1574

3148

4721

6295

7869

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.365

Hom.:

6985

Bravo

AF:

0.348

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.3

(source)

DANN

Benign

0.72

PhyloP100

-1.1

PromoterAI

-0.0098

Neutral

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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