3-119814499-C-T

Variant summary

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

The NM_003889.4(NR1I2):c.795-480C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,980 control chromosomes in the GnomAD database, including 4,796 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 0.24 (4796 hom., cov: 32)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1I2	NM_003889.4	c.795-480C>T		intron_variant		ENST00000393716.8
NR1I2	NM_022002.3	c.912-480C>T		intron_variant
NR1I2	NM_033013.3	c.684-480C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1I2	ENST00000393716.8	c.795-480C>T		intron_variant		1	NM_003889.4	P2
NR1I2	ENST00000337940.4	c.912-480C>T		intron_variant		1		A2
NR1I2	ENST00000466380.6	c.684-480C>T		intron_variant		1		A2
NR1I2	ENST00000493757.1	n.927-480C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36328 AN: 151864 Hom.: 4793 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.239 AC: 36374 AN: 151980 Hom.: 4796 Cov.: 32 AF XY: 0.243 AC XY: 18044 AN XY: 74286

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.223

Alfa AF: 0.194 Hom.: 2884

Bravo AF: 0.237

Asia WGS AF: 0.360 AC: 1250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.0090
Dann	Benign	0.56

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: rs11917714; hg19: chr3-119533346;