rs3732357

Positions:

• chr3-119812011-G-A

Variant summary

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

The NM_003889.4(NR1I2):​c.519+285G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,970 control chromosomes in the GnomAD database, including 27,865 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 0.58 (27865 hom., cov: 31)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119

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 (NFE) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.519+285G>A		intron_variant		ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.636+285G>A		intron_variant			NP_071285.1
NR1I2	NM_033013.3	c.519+285G>A		intron_variant			NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.519+285G>A		intron_variant		1	NM_003889.4	ENSP00000377319	P2
NR1I2	ENST00000337940.4	c.636+285G>A		intron_variant		1		ENSP00000336528	A2
NR1I2	ENST00000466380.6	c.519+285G>A		intron_variant		1		ENSP00000420297	A2
NR1I2	ENST00000493757.1	n.651+285G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88327 AN: 151852 Hom.: 27881 Cov.: 31

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.581 AC: 88322 AN: 151970 Hom.: 27865 Cov.: 31 AF XY: 0.581 AC XY: 43172 AN XY: 74250

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.642

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.601

Alfa AF: 0.680 Hom.: 72842

Bravo AF: 0.577

Asia WGS AF: 0.594 AC: 2066 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.37

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: rs3732357; hg19: chr3-119530858;