NM_003889.4:c.315C>G

Variant names:

• chr3-119810178-C-G
• rs150651210
• NM_003889.4:c.315C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003889.4(NR1I2):​c.315C>G​(p.Ser105Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S105S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NR1I2 NM_003889.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• Publications: 0 publications found

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]

NR1I2 Gene-Disease associations (from GenCC):

• pediatric lymphoma

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.315C>G	p.Ser105Arg	missense_variant	Exon 3 of 9	ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.432C>G	p.Ser144Arg	missense_variant	Exon 3 of 9		NP_071285.1
NR1I2	NM_033013.3	c.315C>G	p.Ser105Arg	missense_variant	Exon 3 of 9		NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.315C>G	p.Ser105Arg	missense_variant	Exon 3 of 9	1	NM_003889.4	ENSP00000377319.3
NR1I2	ENST00000337940.4	c.432C>G	p.Ser144Arg	missense_variant	Exon 3 of 9	1		ENSP00000336528.4
NR1I2	ENST00000466380.6	c.315C>G	p.Ser105Arg	missense_variant	Exon 3 of 9	1		ENSP00000420297.2
NR1I2	ENST00000474090.1	n.603C>G		non_coding_transcript_exon_variant	Exon 3 of 3	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.70	.;.;.;.;D
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.050	N
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.46	T;T;T;T;T
MetaSVM	Uncertain	0.71	D
MutationAssessor	Benign	1.1	.;.;.;L;L
PhyloP100		-2.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.9	N;N;N;.;.
REVEL	Uncertain	0.56
Sift	Uncertain	0.0060	D;D;D;.;.
Sift4G	Uncertain	0.018	D;D;D;.;.
Vest4		0.51
MutPred		0.53		.;.;Gain of MoRF binding (P = 0.0206);.;.;
MVP		0.67
MPC		0.49
ClinPred		0.87	D
GERP RS		-4.3
Varity_R		0.16
gMVP		0.82
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs150651210; hg19: chr3-119529025;