3-119785534-G-A

Position:

• chr3-119785534-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.-23+3234G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 152,012 control chromosomes in the GnomAD database, including 20,371 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 (20371 hom., cov: 31)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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 (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1I2	NM_003889.4	c.-23+3234G>A		intron_variant		ENST00000393716.8
NR1I2	NM_022002.3	c.95+2682G>A		intron_variant
NR1I2	NM_033013.3	c.-23+3234G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1I2	ENST00000393716.8	c.-23+3234G>A		intron_variant		1	NM_003889.4	P2
NR1I2	ENST00000337940.4	c.95+2682G>A		intron_variant		1		A2
NR1I2	ENST00000466380.6	c.-23+3234G>A		intron_variant		1		A2
NR1I2	ENST00000474090.1	n.266+3234G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73655 AN: 151894 Hom.: 20364 Cov.: 31

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.485 AC: 73679 AN: 152012 Hom.: 20371 Cov.: 31 AF XY: 0.492 AC XY: 36515 AN XY: 74284

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.497

Alfa AF: 0.564 Hom.: 30997

Bravo AF: 0.468

Asia WGS AF: 0.659 AC: 2291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.64
DANN	Benign	0.41

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: rs10934498; hg19: chr3-119504381;