3-119810842-C-T

Variant names:

• chr3-119810842-C-T
• rs2472681
• NM_003889.4:c.331+648C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003889.4(NR1I2):​c.331+648C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 152,000 control chromosomes in the GnomAD database, including 28,378 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 0.59 (28378 hom., cov: 32)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936

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 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 = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.331+648C>T		intron_variant	Intron 3 of 8	ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.448+648C>T		intron_variant	Intron 3 of 8		NP_071285.1
NR1I2	NM_033013.3	c.331+648C>T		intron_variant	Intron 3 of 8		NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.331+648C>T		intron_variant	Intron 3 of 8	1	NM_003889.4	ENSP00000377319.3
NR1I2	ENST00000337940.4	c.448+648C>T		intron_variant	Intron 3 of 8	1		ENSP00000336528.4
NR1I2	ENST00000466380.6	c.331+648C>T		intron_variant	Intron 3 of 8	1		ENSP00000420297.2
NR1I2	ENST00000493757.1	n.-234C>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89707 AN: 151882 Hom.: 28387 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.611

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.590 AC: 89721 AN: 152000 Hom.: 28378 Cov.: 32 AF XY: 0.592 AC XY: 44010 AN XY: 74310

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.587

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.610

Alfa AF: 0.649 Hom.: 8207

Bravo AF: 0.586

Asia WGS AF: 0.610 AC: 2123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.53

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: rs2472681; hg19: chr3-119529689;