rs4234666
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_003889.4(NR1I2):c.-23+4170C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000933 in 152,208 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00093 ( 0 hom., cov: 33)
Consequence
NR1I2
NM_003889.4 intron
NM_003889.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.00
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 Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR1I2 | NM_003889.4 | c.-23+4170C>A | intron_variant | ENST00000393716.8 | |||
NR1I2 | NM_022002.3 | c.95+3618C>A | intron_variant | ||||
NR1I2 | NM_033013.3 | c.-23+4170C>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR1I2 | ENST00000393716.8 | c.-23+4170C>A | intron_variant | 1 | NM_003889.4 | P2 | |||
NR1I2 | ENST00000337940.4 | c.95+3618C>A | intron_variant | 1 | A2 | ||||
NR1I2 | ENST00000466380.6 | c.-23+4170C>A | intron_variant | 1 | A2 | ||||
NR1I2 | ENST00000474090.1 | n.266+4170C>A | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000934 AC: 142AN: 152090Hom.: 0 Cov.: 33
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GnomAD4 genome ? AF: 0.000933 AC: 142AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.000994 AC XY: 74AN XY: 74424
GnomAD4 genome
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ClinVar
Not reported inComputational scores
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at