3-119801278-T-C

Position:

• chr3-119801278-T-C

Variant summary

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

The NM_003889.4(NR1I2):​c.-22-5951T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,148 control chromosomes in the GnomAD database, including 26,983 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 (26983 hom., cov: 34)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

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]

ENSG00000285585 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.-22-5951T>C		intron_variant		ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.96-5951T>C		intron_variant			NP_071285.1
NR1I2	NM_033013.3	c.-22-5951T>C		intron_variant			NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.-22-5951T>C		intron_variant		1	NM_003889.4	ENSP00000377319.3
ENSG00000285585	ENST00000648112.1	c.*2-5951T>C		intron_variant				ENSP00000497876.1

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89870 AN: 152030 Hom.: 26960 Cov.: 34

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.591 AC: 89940 AN: 152148 Hom.: 26983 Cov.: 34 AF XY: 0.596 AC XY: 44331 AN XY: 74388

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.578

Alfa AF: 0.617 Hom.: 40298

Bravo AF: 0.574

Asia WGS AF: 0.611 AC: 2129 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	11
DANN	Benign	0.72

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: rs2461823; hg19: chr3-119520125;