chr3-119811601-C-G

Variant names:

• chr3-119811601-C-G
• rs772838074
• NM_003889.4:c.394C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003889.4(NR1I2):​c.394C>G​(p.Arg132Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NR1I2 NM_003889.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08059788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.394C>G	p.Arg132Gly	missense_variant	Exon 4 of 9	ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.511C>G	p.Arg171Gly	missense_variant	Exon 4 of 9		NP_071285.1
NR1I2	NM_033013.3	c.394C>G	p.Arg132Gly	missense_variant	Exon 4 of 9		NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.394C>G	p.Arg132Gly	missense_variant	Exon 4 of 9	1	NM_003889.4	ENSP00000377319.3
NR1I2	ENST00000337940.4	c.511C>G	p.Arg171Gly	missense_variant	Exon 4 of 9	1		ENSP00000336528.4
NR1I2	ENST00000466380.6	c.394C>G	p.Arg132Gly	missense_variant	Exon 4 of 9	1		ENSP00000420297.2
NR1I2	ENST00000493757.1	n.526C>G		non_coding_transcript_exon_variant	Exon 1 of 6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	7.7
DANN	Benign	0.96
DEOGEN2	Benign	0.23	.;.;.;.;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.61	T;T;T;T;T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.081	T;T;T;T;T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.4	.;.;.;M;M
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.5	D;D;D;.;.
REVEL	Benign	0.10
Sift	Benign	0.094	T;T;T;.;.
Sift4G	Benign	0.17	T;T;T;.;.
Polyphen		0.095	.;.;.;.;B
Vest4		0.22
MutPred		0.34		Gain of glycosylation at S130 (P = 7e-04);Gain of glycosylation at S130 (P = 7e-04);.;Gain of glycosylation at S130 (P = 7e-04);Gain of glycosylation at S130 (P = 7e-04);
MVP		0.67
MPC		0.11
ClinPred		0.080	T
GERP RS		1.9
Varity_R		0.083
gMVP		0.52

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

Other links and lift over

dbSNP: rs772838074; hg19: chr3-119530448;