chr3-119807525-G-A

Position:

• chr3-119807525-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.197+78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,278,430 control chromosomes in the GnomAD database, including 268,371 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 0.56 (25871 hom., cov: 32)
  • Exomes 𝑓: 0.65 (242500 hom.)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.197+78G>A		intron_variant		ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.314+78G>A		intron_variant			NP_071285.1
NR1I2	NM_033013.3	c.197+78G>A		intron_variant			NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.197+78G>A		intron_variant		1	NM_003889.4	ENSP00000377319	P2
NR1I2	ENST00000337940.4	c.314+78G>A		intron_variant		1		ENSP00000336528	A2
NR1I2	ENST00000466380.6	c.197+78G>A		intron_variant		1		ENSP00000420297	A2
NR1I2	ENST00000474090.1	n.485+78G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85429 AN: 151946 Hom.: 25879 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.579

GnomAD4 exome AF: 0.652 AC: 733890 AN: 1126366 Hom.: 242500 AF XY: 0.650 AC XY: 372868 AN XY: 573722

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.719

Gnomad4 ASJ exome AF: 0.677

Gnomad4 EAS exome AF: 0.585

Gnomad4 SAS exome AF: 0.584

Gnomad4 FIN exome AF: 0.616

Gnomad4 NFE exome AF: 0.672

Gnomad4 OTH exome AF: 0.632

GnomAD4 genome AF: 0.562 AC: 85440 AN: 152064 Hom.: 25871 Cov.: 32 AF XY: 0.564 AC XY: 41899 AN XY: 74322

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.579

Alfa AF: 0.614 Hom.: 5936

Bravo AF: 0.559

Asia WGS AF: 0.586 AC: 2040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.0
DANN	Benign	0.82

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: rs1464602; hg19: chr3-119526372;