Menu
GeneBe

3-119811699-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_003889.4(NR1I2):c.492T>C(p.Thr164=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 1,612,596 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 79 hom., cov: 32)
Exomes 𝑓: 0.0017 ( 71 hom. )

Consequence

NR1I2
NM_003889.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.170
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 -15 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=-0.62).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-119811699-T-C is Benign according to our data. Variant chr3-119811699-T-C is described in ClinVar as [Benign]. Clinvar id is 775899.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=0.17 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0569 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NR1I2NM_003889.4 linkuse as main transcriptc.492T>C p.Thr164= synonymous_variant 4/9 ENST00000393716.8
NR1I2NM_022002.3 linkuse as main transcriptc.609T>C p.Thr203= synonymous_variant 4/9
NR1I2NM_033013.3 linkuse as main transcriptc.492T>C p.Thr164= synonymous_variant 4/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NR1I2ENST00000393716.8 linkuse as main transcriptc.492T>C p.Thr164= synonymous_variant 4/91 NM_003889.4 P2O75469-1
NR1I2ENST00000337940.4 linkuse as main transcriptc.609T>C p.Thr203= synonymous_variant 4/91 A2O75469-7
NR1I2ENST00000466380.6 linkuse as main transcriptc.492T>C p.Thr164= synonymous_variant 4/91 A2O75469-4
NR1I2ENST00000493757.1 linkuse as main transcriptn.624T>C non_coding_transcript_exon_variant 1/62

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0176
AC:
2675
AN:
152176
Hom.:
78
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0588
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0132
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:
0.0000882
Gnomad OTH
AF:
0.0148
GnomAD3 exomes
AF:
0.00456
AC:
1127
AN:
246910
Hom.:
26
AF XY:
0.00317
AC XY:
424
AN XY:
133560
show subpopulations
Gnomad AFR exome
AF:
0.0586
Gnomad AMR exome
AF:
0.00479
Gnomad ASJ exome
AF:
0.000301
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000133
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000152
Gnomad OTH exome
AF:
0.00232
GnomAD4 exome
AF:
0.00174
AC:
2541
AN:
1460302
Hom.:
71
Cov.:
31
AF XY:
0.00143
AC XY:
1039
AN XY:
726260
show subpopulations
Gnomad4 AFR exome
AF:
0.0566
Gnomad4 AMR exome
AF:
0.00528
Gnomad4 ASJ exome
AF:
0.000422
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000932
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000141
Gnomad4 OTH exome
AF:
0.00385
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0176
AC:
2682
AN:
152294
Hom.:
79
Cov.:
32
AF XY:
0.0170
AC XY:
1265
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.0588
Gnomad4 AMR
AF:
0.0132
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.0147
Alfa
AF:
0.00408
Hom.:
25
Bravo
AF:
0.0199
Asia WGS
AF:
0.00318
AC:
11
AN:
3478

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 testingInvitaeAug 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
Cadd
Benign
11
Dann
Benign
0.63
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8

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: rs12721611; hg19: chr3-119530546; API