3-119810842-C-T

Variant summary

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

The NM_003889.4(NR1I2):​c.331+648C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 152,000 control chromosomes in the GnomAD database, including 28,378 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 0.59 ( 28378 hom., cov: 32)

Consequence

NR1I2
NM_003889.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.936
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=-0.83).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NR1I2NM_003889.4 linkc.331+648C>T intron_variant Intron 3 of 8 ENST00000393716.8 NP_003880.3 O75469-1
NR1I2NM_022002.3 linkc.448+648C>T intron_variant Intron 3 of 8 NP_071285.1 O75469-7F1D8P9
NR1I2NM_033013.3 linkc.331+648C>T intron_variant Intron 3 of 8 NP_148934.1 O75469-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NR1I2ENST00000393716.8 linkc.331+648C>T intron_variant Intron 3 of 8 1 NM_003889.4 ENSP00000377319.3 O75469-1J3KPQ3
NR1I2ENST00000337940.4 linkc.448+648C>T intron_variant Intron 3 of 8 1 ENSP00000336528.4 O75469-7
NR1I2ENST00000466380.6 linkc.331+648C>T intron_variant Intron 3 of 8 1 ENSP00000420297.2 O75469-4H0Y8E2
NR1I2ENST00000493757.1 linkn.-234C>T upstream_gene_variant 2

Frequencies

GnomAD3 genomes
AF:
0.591
AC:
89707
AN:
151882
Hom.:
28387
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.339
Gnomad AMI
AF:
0.781
Gnomad AMR
AF:
0.695
Gnomad ASJ
AF:
0.690
Gnomad EAS
AF:
0.672
Gnomad SAS
AF:
0.587
Gnomad FIN
AF:
0.643
Gnomad MID
AF:
0.640
Gnomad NFE
AF:
0.698
Gnomad OTH
AF:
0.611
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.590
AC:
89721
AN:
152000
Hom.:
28378
Cov.:
32
AF XY:
0.592
AC XY:
44010
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.339
Gnomad4 AMR
AF:
0.694
Gnomad4 ASJ
AF:
0.690
Gnomad4 EAS
AF:
0.673
Gnomad4 SAS
AF:
0.587
Gnomad4 FIN
AF:
0.643
Gnomad4 NFE
AF:
0.698
Gnomad4 OTH
AF:
0.610
Alfa
AF:
0.649
Hom.:
8207
Bravo
AF:
0.586
Asia WGS
AF:
0.610
AC:
2123
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
2.2
DANN
Benign
0.53

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: rs2472681; hg19: chr3-119529689; API