dbSNP rs1523127: NR1I2:n.158C>A (chr3-119782192-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000474090.1(NR1I2):n.158C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 154,076 control chromosomes in the GnomAD database, including 21,543 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 0.49 ( 21320 hom., cov: 33)

Exomes 𝑓: 0.47 ( 223 hom. )

Consequence

NR1I2
ENST00000474090.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.925

Publications

54 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=-0.74).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1I2	NM_003889.4 link	c.-131C>A		5_prime_UTR_variant	Exon 1 of 9	ENST00000393716.8	NP_003880.3	O75469-1
NR1I2	NM_033013.3 link	c.-131C>A		5_prime_UTR_variant	Exon 1 of 9		NP_148934.1	O75469-4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NR1I2	ENST00000474090.1 link	n.158C>A	non_coding_transcript_exon_variant	Exon 1 of 3	1
NR1I2	ENST00000393716.8 link	c.-131C>A	5_prime_UTR_variant	Exon 1 of 9	1	NM_003889.4	ENSP00000377319.3	O75469-1J3KPQ3
NR1I2	ENST00000466380.6 link	c.-131C>A	5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000420297.2	O75469-4H0Y8E2
ENSG00000285585	ENST00000648112.1 link	c.*2-25037C>A	intron_variant	Intron 17 of 17			ENSP00000497876.1

Frequencies

GnomAD3 genomes

AF:

0.494

AC:

75052

AN:

152040

Hom.:

21318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.568

Gnomad ASJ

AF:

0.498

Gnomad EAS

AF:

0.778

Gnomad SAS

AF:

0.596

Gnomad FIN

AF:

0.630

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.607

Gnomad OTH

AF:

0.514

GnomAD4 exome

AF:

0.466

AC:

894

AN:

1918

Hom.:

223

Cov.:

AF XY:

0.489

AC XY:

488

AN XY:

998

show subpopulations

African (AFR)

AF:

0.133

AC:

AN:

American (AMR)

AF:

0.417

AC:

186

AN:

446

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

AN:

East Asian (EAS)

AF:

0.621

AC:

AN:

South Asian (SAS)

AF:

0.466

AC:

AN:

116

European-Finnish (FIN)

AF:

0.417

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.483

AC:

574

AN:

1188

Other (OTH)

AF:

0.533

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.493

AC:

75072

AN:

152158

Hom.:

21320

Cov.:

AF XY:

0.500

AC XY:

37226

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.194

AC:

8061

AN:

41530

American (AMR)

AF:

0.569

AC:

8694

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.498

AC:

1726

AN:

3468

East Asian (EAS)

AF:

0.777

AC:

4015

AN:

5164

South Asian (SAS)

AF:

0.597

AC:

2878

AN:

4824

European-Finnish (FIN)

AF:

0.630

AC:

6678

AN:

10592

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.607

AC:

41288

AN:

67980

Other (OTH)

AF:

0.518

AC:

1090

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1722

3445

5167

6890

8612

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<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:

0.573

Hom.:

109881

Bravo

AF:

0.476

Asia WGS

AF:

0.679

AC:

2362

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.4

(source)

DANN

Benign

0.84

PhyloP100

0.93

PromoterAI

-0.017

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over