chr3-119812862-C-T
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_003889.4(NR1I2):c.696C>T(p.Gly232=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00845 in 1,614,180 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0063 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0087 ( 80 hom. )
Consequence
NR1I2
NM_003889.4 synonymous
NM_003889.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -8.17
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 -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 3-119812862-C-T is Benign according to our data. Variant chr3-119812862-C-T is described in ClinVar as [Benign]. Clinvar id is 787169.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-8.17 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR1I2 | NM_003889.4 | c.696C>T | p.Gly232= | synonymous_variant | 5/9 | ENST00000393716.8 | |
NR1I2 | NM_022002.3 | c.813C>T | p.Gly271= | synonymous_variant | 5/9 | ||
NR1I2 | NM_033013.3 | c.585C>T | p.Gly195= | synonymous_variant | 5/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR1I2 | ENST00000393716.8 | c.696C>T | p.Gly232= | synonymous_variant | 5/9 | 1 | NM_003889.4 | P2 | |
NR1I2 | ENST00000337940.4 | c.813C>T | p.Gly271= | synonymous_variant | 5/9 | 1 | A2 | ||
NR1I2 | ENST00000466380.6 | c.585C>T | p.Gly195= | synonymous_variant | 5/9 | 1 | A2 | ||
NR1I2 | ENST00000493757.1 | n.828C>T | non_coding_transcript_exon_variant | 2/6 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00630 AC: 959AN: 152188Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00651 AC: 1633AN: 251016Hom.: 11 AF XY: 0.00642 AC XY: 871AN XY: 135698
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GnomAD4 exome AF: 0.00868 AC: 12687AN: 1461874Hom.: 80 Cov.: 32 AF XY: 0.00848 AC XY: 6167AN XY: 727240
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GnomAD4 genome AF: 0.00630 AC: 960AN: 152306Hom.: 6 Cov.: 32 AF XY: 0.00583 AC XY: 434AN XY: 74474
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 21, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at