rs2461817

Positions:

• chr3-119805804-A-C
• chr3-119805804-A-G

Variant summary

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

The NM_003889.4(NR1I2):​c.-22-1425A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 150,808 control chromosomes in the GnomAD database, including 23,668 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 0.55 (23668 hom., cov: 27)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542

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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.-22-1425A>C		intron_variant		ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.96-1425A>C		intron_variant			NP_071285.1
NR1I2	NM_033013.3	c.-22-1425A>C		intron_variant			NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.-22-1425A>C		intron_variant		1	NM_003889.4	ENSP00000377319	P2
NR1I2	ENST00000337940.4	c.96-1425A>C		intron_variant		1		ENSP00000336528	A2
NR1I2	ENST00000466380.6	c.-22-1425A>C		intron_variant		1		ENSP00000420297	A2
NR1I2	ENST00000474090.1	n.267-1425A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83214 AN: 150690 Hom.: 23660 Cov.: 27

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.552 AC: 83264 AN: 150808 Hom.: 23668 Cov.: 27 AF XY: 0.558 AC XY: 41077 AN XY: 73558

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.539

Alfa AF: 0.591 Hom.: 25877

Bravo AF: 0.534

Asia WGS AF: 0.576 AC: 2004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.88

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: rs2461817; hg19: chr3-119524651;