rs6438550

Positions:

• chr3-119817970-G-A
• chr3-119817970-G-C

Variant summary

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

The NM_003889.4(NR1I2):​c.*758G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 985,340 control chromosomes in the GnomAD database, including 438,608 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 0.92 (64795 hom., cov: 32)
  • Exomes 𝑓: 0.95 (373813 hom.)
• Consequence: NR1I2 NM_003889.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209

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 (AMR) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1I2	NM_003889.4	c.*758G>A		3_prime_UTR_variant	9/9	ENST00000393716.8
NR1I2	NM_022002.3	c.*758G>A		3_prime_UTR_variant	9/9
NR1I2	NM_033013.3	c.*758G>A		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1I2	ENST00000393716.8	c.*758G>A		3_prime_UTR_variant	9/9	1	NM_003889.4	P2
NR1I2	ENST00000337940.4	c.*758G>A		3_prime_UTR_variant	9/9	1		A2
NR1I2	ENST00000466380.6	c.*758G>A		3_prime_UTR_variant	9/9	1		A2
NR1I2	ENST00000493757.1	n.2195G>A		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.922 AC: 140228 AN: 152144 Hom.: 64744 Cov.: 32

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.954

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.948

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.925

GnomAD4 exome AF: 0.947 AC: 789039 AN: 833078 Hom.: 373813 Cov.: 26 AF XY: 0.948 AC XY: 364531 AN XY: 384720

Gnomad4 AFR exome AF: 0.849

Gnomad4 AMR exome AF: 0.971

Gnomad4 ASJ exome AF: 0.951

Gnomad4 EAS exome AF: 0.909

Gnomad4 SAS exome AF: 0.874

Gnomad4 FIN exome AF: 0.929

Gnomad4 NFE exome AF: 0.951

Gnomad4 OTH exome AF: 0.933

GnomAD4 genome AF: 0.922 AC: 140340 AN: 152262 Hom.: 64795 Cov.: 32 AF XY: 0.921 AC XY: 68550 AN XY: 74442

Gnomad4 AFR AF: 0.865

Gnomad4 AMR AF: 0.954

Gnomad4 ASJ AF: 0.956

Gnomad4 EAS AF: 0.914

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.948

Gnomad4 NFE AF: 0.947

Gnomad4 OTH AF: 0.922

Alfa AF: 0.944 Hom.: 110614

Bravo AF: 0.922

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.55

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: rs6438550; hg19: chr3-119536817;