rs3842689

Positions:

• chr3-119782550-CAGGAGA-C
• chr3-119782550-CAGGAGA-CAGGAGAAGGAGA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_003889.4(NR1I2):​c.-23+253_-23+258delGAGAAG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (9580 hom., cov: 0)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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]

ENSG00000285585 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.-23+253_-23+258delGAGAAG		intron_variant		ENST00000393716.8	NP_003880.3
NR1I2	NM_033013.3	c.-23+253_-23+258delGAGAAG		intron_variant			NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.-23+253_-23+258delGAGAAG		intron_variant		1	NM_003889.4	ENSP00000377319.3
ENSG00000285585	ENST00000648112.1	c.*2-24676_*2-24671delGAGAAG		intron_variant				ENSP00000497876.1
NR1I2	ENST00000466380.6	c.-23+253_-23+258delGAGAAG		intron_variant		1		ENSP00000420297.2
NR1I2	ENST00000474090.1	n.266+253_266+258delGAGAAG		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53147 AN: 151488 Hom.: 9577 Cov.: 0

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.351 AC: 53175 AN: 151606 Hom.: 9580 Cov.: 0 AF XY: 0.349 AC XY: 25842 AN XY: 74072

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.358

Alfa AF: 0.375 Hom.: 1277

Bravo AF: 0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3842689; hg19: chr3-119501397;