Variant 3-119811695-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003889.4(NR1I2):c.488A>G(p.Asp163Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,612,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

NR1I2
NM_003889.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.16

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.911

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NR1I2	NM_003889.4 linkuse as main transcript	c.488A>G	p.Asp163Gly	missense_variant	4/9	ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3 linkuse as main transcript	c.605A>G	p.Asp202Gly	missense_variant	4/9		NP_071285.1
NR1I2	NM_033013.3 linkuse as main transcript	c.488A>G	p.Asp163Gly	missense_variant	4/9		NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8 linkuse as main transcript	c.488A>G	p.Asp163Gly	missense_variant	4/9	1	NM_003889.4	ENSP00000377319	P2	O75469-1
NR1I2	ENST00000337940.4 linkuse as main transcript	c.605A>G	p.Asp202Gly	missense_variant	4/9	1		ENSP00000336528	A2	O75469-7
NR1I2	ENST00000466380.6 linkuse as main transcript	c.488A>G	p.Asp163Gly	missense_variant	4/9	1		ENSP00000420297	A2	O75469-4
NR1I2	ENST00000493757.1 linkuse as main transcript	n.620A>G		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247676

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133942

show subpopulations

Gnomad AFR exome

AF:

0.000189

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1460656

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726440

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000436

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

.;.;.;.;T

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

D;D;D;D;D

M_CAP

Pathogenic

0.32

MetaRNN

Pathogenic

0.91

D;D;D;D;D

MetaSVM

Pathogenic

0.87

MutationAssessor

Uncertain

2.3

.;.;.;M;M

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-4.1

D;D;D;.;.

REVEL

Pathogenic

0.87

Sift

Benign

0.072

T;T;T;.;.

Sift4G

Benign

0.23

T;T;T;.;.

Polyphen

1.0

.;.;.;.;D

Vest4

0.73

MVP

0.96

MPC

0.52

ClinPred

0.97

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.70

gMVP

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over