Menu
GeneBe

3-119812862-C-T

Variant summary

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

The NM_003889.4(NR1I2):c.696C>T(p.Gly232=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00845 in 1,614,180 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0087 ( 80 hom. )

Consequence

NR1I2
NM_003889.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -8.17
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-119812862-C-T is Benign according to our data. Variant chr3-119812862-C-T is described in ClinVar as [Benign]. Clinvar id is 787169.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-8.17 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NR1I2NM_003889.4 linkuse as main transcriptc.696C>T p.Gly232= synonymous_variant 5/9 ENST00000393716.8
NR1I2NM_022002.3 linkuse as main transcriptc.813C>T p.Gly271= synonymous_variant 5/9
NR1I2NM_033013.3 linkuse as main transcriptc.585C>T p.Gly195= synonymous_variant 5/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NR1I2ENST00000393716.8 linkuse as main transcriptc.696C>T p.Gly232= synonymous_variant 5/91 NM_003889.4 P2O75469-1
NR1I2ENST00000337940.4 linkuse as main transcriptc.813C>T p.Gly271= synonymous_variant 5/91 A2O75469-7
NR1I2ENST00000466380.6 linkuse as main transcriptc.585C>T p.Gly195= synonymous_variant 5/91 A2O75469-4
NR1I2ENST00000493757.1 linkuse as main transcriptn.828C>T non_coding_transcript_exon_variant 2/62

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00630
AC:
959
AN:
152188
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00229
Gnomad AMI
AF:
0.0296
Gnomad AMR
AF:
0.00687
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000769
Gnomad SAS
AF:
0.00186
Gnomad FIN
AF:
0.00245
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00991
Gnomad OTH
AF:
0.00813
GnomAD3 exomes
AF:
0.00651
AC:
1633
AN:
251016
Hom.:
11
AF XY:
0.00642
AC XY:
871
AN XY:
135698
show subpopulations
Gnomad AFR exome
AF:
0.00154
Gnomad AMR exome
AF:
0.00466
Gnomad ASJ exome
AF:
0.0000993
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00222
Gnomad FIN exome
AF:
0.00328
Gnomad NFE exome
AF:
0.0111
Gnomad OTH exome
AF:
0.00767
GnomAD4 exome
AF:
0.00868
AC:
12687
AN:
1461874
Hom.:
80
Cov.:
32
AF XY:
0.00848
AC XY:
6167
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00137
Gnomad4 AMR exome
AF:
0.00532
Gnomad4 ASJ exome
AF:
0.000230
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00255
Gnomad4 FIN exome
AF:
0.00344
Gnomad4 NFE exome
AF:
0.0103
Gnomad4 OTH exome
AF:
0.00800
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00630
AC:
960
AN:
152306
Hom.:
6
Cov.:
32
AF XY:
0.00583
AC XY:
434
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.00229
Gnomad4 AMR
AF:
0.00686
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000771
Gnomad4 SAS
AF:
0.00207
Gnomad4 FIN
AF:
0.00245
Gnomad4 NFE
AF:
0.00991
Gnomad4 OTH
AF:
0.00804
Alfa
AF:
0.00855
Hom.:
4
Bravo
AF:
0.00670
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.00927
EpiControl
AF:
0.0120

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 21, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
Cadd
Benign
0.19
Dann
Benign
0.35

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.

Other links and lift over

dbSNP: rs61755051; hg19: chr3-119531709; API