chr3-119814409-G-C

Variant summary

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

The NM_003889.4(NR1I2):​c.795-570G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,032 control chromosomes in the GnomAD database, including 20,406 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 0.48 ( 20406 hom., cov: 32)

Consequence

NR1I2
NM_003889.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.168
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=-0.58).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NR1I2NM_003889.4 linkuse as main transcriptc.795-570G>C intron_variant ENST00000393716.8
NR1I2NM_022002.3 linkuse as main transcriptc.912-570G>C intron_variant
NR1I2NM_033013.3 linkuse as main transcriptc.684-570G>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NR1I2ENST00000393716.8 linkuse as main transcriptc.795-570G>C intron_variant 1 NM_003889.4 P2O75469-1
NR1I2ENST00000337940.4 linkuse as main transcriptc.912-570G>C intron_variant 1 A2O75469-7
NR1I2ENST00000466380.6 linkuse as main transcriptc.684-570G>C intron_variant 1 A2O75469-4
NR1I2ENST00000493757.1 linkuse as main transcriptn.927-570G>C intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.484
AC:
73489
AN:
151914
Hom.:
20400
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.195
Gnomad AMI
AF:
0.660
Gnomad AMR
AF:
0.587
Gnomad ASJ
AF:
0.612
Gnomad EAS
AF:
0.429
Gnomad SAS
AF:
0.508
Gnomad FIN
AF:
0.614
Gnomad MID
AF:
0.538
Gnomad NFE
AF:
0.609
Gnomad OTH
AF:
0.496
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.484
AC:
73521
AN:
152032
Hom.:
20406
Cov.:
32
AF XY:
0.487
AC XY:
36155
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.196
Gnomad4 AMR
AF:
0.586
Gnomad4 ASJ
AF:
0.612
Gnomad4 EAS
AF:
0.429
Gnomad4 SAS
AF:
0.509
Gnomad4 FIN
AF:
0.614
Gnomad4 NFE
AF:
0.609
Gnomad4 OTH
AF:
0.495
Alfa
AF:
0.520
Hom.:
2702
Bravo
AF:
0.472
Asia WGS
AF:
0.446
AC:
1556
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
CADD
Benign
4.5
DANN
Benign
0.61

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: rs6784598; hg19: chr3-119533256; API