3-119799570-C-T

Variant names:

• chr3-119799570-C-T
• rs2472677
• NM_003889.4:c.-22-7659C>T

Variant summary

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

The NM_003889.4(NR1I2):​c.-22-7659C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 151,860 control chromosomes in the GnomAD database, including 22,633 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 0.54 (22633 hom., cov: 33)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193

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=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.-22-7659C>T		intron_variant	Intron 1 of 8	ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.96-7659C>T		intron_variant	Intron 1 of 8		NP_071285.1
NR1I2	NM_033013.3	c.-22-7659C>T		intron_variant	Intron 1 of 8		NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.-22-7659C>T		intron_variant	Intron 1 of 8	1	NM_003889.4	ENSP00000377319.3
ENSG00000285585	ENST00000648112.1	c.*2-7659C>T		intron_variant	Intron 17 of 17			ENSP00000497876.1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81404 AN: 151744 Hom.: 22627 Cov.: 33

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.536 AC: 81448 AN: 151860 Hom.: 22633 Cov.: 33 AF XY: 0.543 AC XY: 40321 AN XY: 74226

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.527

Alfa AF: 0.449 Hom.: 1405

Bravo AF: 0.517

Asia WGS AF: 0.565 AC: 1967 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.5
DANN	Benign	0.94

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: rs2472677; hg19: chr3-119518417;