3-119790534-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003889.4(NR1I2):​c.-23+8234A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,048 control chromosomes in the GnomAD database, including 9,819 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 0.35 ( 9819 hom., cov: 32)

Consequence

NR1I2
NM_003889.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.653
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.02).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NR1I2NM_003889.4 linkc.-23+8234A>G intron_variant Intron 1 of 8 ENST00000393716.8 NP_003880.3 O75469-1
NR1I2NM_022002.3 linkc.95+7682A>G intron_variant Intron 1 of 8 NP_071285.1 O75469-7F1D8P9
NR1I2NM_033013.3 linkc.-23+8234A>G intron_variant Intron 1 of 8 NP_148934.1 O75469-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NR1I2ENST00000393716.8 linkc.-23+8234A>G intron_variant Intron 1 of 8 1 NM_003889.4 ENSP00000377319.3 O75469-1J3KPQ3
ENSG00000285585ENST00000648112.1 linkc.*2-16695A>G intron_variant Intron 17 of 17 ENSP00000497876.1

Frequencies

GnomAD3 genomes
AF:
0.350
AC:
53235
AN:
151930
Hom.:
9802
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.419
Gnomad AMI
AF:
0.251
Gnomad AMR
AF:
0.405
Gnomad ASJ
AF:
0.228
Gnomad EAS
AF:
0.379
Gnomad SAS
AF:
0.364
Gnomad FIN
AF:
0.257
Gnomad MID
AF:
0.316
Gnomad NFE
AF:
0.315
Gnomad OTH
AF:
0.351
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.351
AC:
53301
AN:
152048
Hom.:
9819
Cov.:
32
AF XY:
0.347
AC XY:
25806
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.420
Gnomad4 AMR
AF:
0.405
Gnomad4 ASJ
AF:
0.228
Gnomad4 EAS
AF:
0.380
Gnomad4 SAS
AF:
0.364
Gnomad4 FIN
AF:
0.257
Gnomad4 NFE
AF:
0.315
Gnomad4 OTH
AF:
0.349
Alfa
AF:
0.322
Hom.:
11863
Bravo
AF:
0.367
Asia WGS
AF:
0.389
AC:
1351
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.35
DANN
Benign
0.40

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: rs1403526; hg19: chr3-119509381; API