3-119814409-G-C

Position:

• chr3-119814409-G-C

Variant summary

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

The NM_003889.4(NR1I2):​c.795-570G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,032 control chromosomes in the GnomAD database, including 20,406 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 0.48 (20406 hom., cov: 32)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168

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=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1I2	NM_003889.4	c.795-570G>C		intron_variant		ENST00000393716.8
NR1I2	NM_022002.3	c.912-570G>C		intron_variant
NR1I2	NM_033013.3	c.684-570G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1I2	ENST00000393716.8	c.795-570G>C		intron_variant		1	NM_003889.4	P2
NR1I2	ENST00000337940.4	c.912-570G>C		intron_variant		1		A2
NR1I2	ENST00000466380.6	c.684-570G>C		intron_variant		1		A2
NR1I2	ENST00000493757.1	n.927-570G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73489 AN: 151914 Hom.: 20400 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.484 AC: 73521 AN: 152032 Hom.: 20406 Cov.: 32 AF XY: 0.487 AC XY: 36155 AN XY: 74298

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.495

Alfa AF: 0.520 Hom.: 2702

Bravo AF: 0.472

Asia WGS AF: 0.446 AC: 1556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.5
DANN	Benign	0.61

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: rs6784598; hg19: chr3-119533256;