rs6785049

Positions:

• chr3-119814886-G-A
• chr3-119814886-G-T

Variant summary

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

The NM_003889.4(NR1I2):​c.795-93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,522,460 control chromosomes in the GnomAD database, including 264,234 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 0.46 (19763 hom., cov: 32)
  • Exomes 𝑓: 0.59 (244471 hom.)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.58

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 = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1I2	NM_003889.4	c.795-93G>A		intron_variant		ENST00000393716.8
NR1I2	NM_022002.3	c.912-93G>A		intron_variant
NR1I2	NM_033013.3	c.684-93G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1I2	ENST00000393716.8	c.795-93G>A		intron_variant		1	NM_003889.4	P2
NR1I2	ENST00000337940.4	c.912-93G>A		intron_variant		1		A2
NR1I2	ENST00000466380.6	c.684-93G>A		intron_variant		1		A2
NR1I2	ENST00000493757.1	n.927-93G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70065 AN: 151908 Hom.: 19765 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.480

GnomAD4 exome AF: 0.590 AC: 808743 AN: 1370434 Hom.: 244471 AF XY: 0.589 AC XY: 403256 AN XY: 685206

Gnomad4 AFR exome AF: 0.0978

Gnomad4 AMR exome AF: 0.656

Gnomad4 ASJ exome AF: 0.602

Gnomad4 EAS exome AF: 0.430

Gnomad4 SAS exome AF: 0.520

Gnomad4 FIN exome AF: 0.608

Gnomad4 NFE exome AF: 0.615

Gnomad4 OTH exome AF: 0.554

GnomAD4 genome AF: 0.461 AC: 70061 AN: 152026 Hom.: 19763 Cov.: 32 AF XY: 0.464 AC XY: 34474 AN XY: 74302

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.479

Alfa AF: 0.583 Hom.: 29943

Bravo AF: 0.446

Asia WGS AF: 0.428 AC: 1493 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	0.0080
DANN	Benign	0.54

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: rs6785049; hg19: chr3-119533733;