Variant rs12721600 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003889.4(NR1I2):c.543C>T(p.Gly181=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,614,126 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 29 hom. )

Consequence

NR1I2
NM_003889.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.475

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 3-119812709-C-T is Benign according to our data. Variant chr3-119812709-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654059.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.475 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NR1I2	NM_003889.4 linkuse as main transcript	c.543C>T	p.Gly181=	synonymous_variant	5/9	ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3 linkuse as main transcript	c.660C>T	p.Gly220=	synonymous_variant	5/9		NP_071285.1
NR1I2	NM_033013.3 linkuse as main transcript	c.520-88C>T		intron_variant			NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8 linkuse as main transcript	c.543C>T	p.Gly181=	synonymous_variant	5/9	1	NM_003889.4	ENSP00000377319	P2	O75469-1
NR1I2	ENST00000337940.4 linkuse as main transcript	c.660C>T	p.Gly220=	synonymous_variant	5/9	1		ENSP00000336528	A2	O75469-7
NR1I2	ENST00000466380.6 linkuse as main transcript	c.520-88C>T		intron_variant		1		ENSP00000420297	A2	O75469-4
NR1I2	ENST00000493757.1 linkuse as main transcript	n.675C>T		non_coding_transcript_exon_variant	2/6	2

Frequencies

GnomAD3 genomes

AF:

0.00263

AC:

401

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00310

AC:

780

AN:

251374

Hom.:

AF XY:

0.00292

AC XY:

397

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0293

Gnomad NFE exome

AF:

0.00111

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00142

AC:

2069

AN:

1461790

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

1018

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0296

Gnomad4 NFE exome

AF:

0.000369

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.00263

AC:

401

AN:

152336

Hom.:

Cov.:

AF XY:

0.00360

AC XY:

268

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0283

Gnomad4 NFE

AF:

0.00143

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00148

Hom.:

Bravo

AF:

0.000280

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

NR1I2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.2

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over