chr3-119810266-G-T
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_003889.4(NR1I2):c.331+72G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 1,538,278 control chromosomes in the GnomAD database, including 650,455 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 0.87 ( 58693 hom., cov: 35)
Exomes 𝑓: 0.92 ( 591762 hom. )
Consequence
NR1I2
NM_003889.4 intron
NM_003889.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.42
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 = 0.922 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NR1I2 | NM_003889.4 | c.331+72G>T | intron_variant | ENST00000393716.8 | NP_003880.3 | |||
NR1I2 | NM_022002.3 | c.448+72G>T | intron_variant | NP_071285.1 | ||||
NR1I2 | NM_033013.3 | c.331+72G>T | intron_variant | NP_148934.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NR1I2 | ENST00000393716.8 | c.331+72G>T | intron_variant | 1 | NM_003889.4 | ENSP00000377319.3 | ||||
NR1I2 | ENST00000337940.4 | c.448+72G>T | intron_variant | 1 | ENSP00000336528.4 | |||||
NR1I2 | ENST00000466380.6 | c.331+72G>T | intron_variant | 1 | ENSP00000420297.2 | |||||
NR1I2 | ENST00000474090.1 | n.691G>T | non_coding_transcript_exon_variant | 3/3 | 1 |
Frequencies
GnomAD3 genomes AF: 0.874 AC: 133003AN: 152120Hom.: 58668 Cov.: 35
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GnomAD4 exome AF: 0.923 AC: 1279707AN: 1386040Hom.: 591762 Cov.: 33 AF XY: 0.922 AC XY: 629138AN XY: 682164
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GnomAD4 genome AF: 0.874 AC: 133079AN: 152238Hom.: 58693 Cov.: 35 AF XY: 0.874 AC XY: 65090AN XY: 74442
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at