rs10511395

Positions:

• chr3-119817712-C-A

Variant summary

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

The NM_003889.4(NR1I2):​c.*500C>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 0.153 in 1,070,120 control chromosomes in the GnomAD database, including 12,897 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 0.13 (1471 hom., cov: 33)
  • Exomes 𝑓: 0.16 (11426 hom.)
• Consequence: NR1I2 NM_003889.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1I2	NM_003889.4	c.*500C>A		3_prime_UTR_variant	9/9	ENST00000393716.8
NR1I2	NM_022002.3	c.*500C>A		3_prime_UTR_variant	9/9
NR1I2	NM_033013.3	c.*500C>A		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1I2	ENST00000393716.8	c.*500C>A		3_prime_UTR_variant	9/9	1	NM_003889.4	P2
NR1I2	ENST00000337940.4	c.*500C>A		3_prime_UTR_variant	9/9	1		A2
NR1I2	ENST00000466380.6	c.*500C>A		3_prime_UTR_variant	9/9	1		A2
NR1I2	ENST00000493757.1	n.1937C>A		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20217 AN: 152094 Hom.: 1471 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0615

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.156 AC: 143649 AN: 917908 Hom.: 11426 Cov.: 38 AF XY: 0.156 AC XY: 66967 AN XY: 428318

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.000969

Gnomad4 SAS exome AF: 0.0835

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.133 AC: 20224 AN: 152212 Hom.: 1471 Cov.: 33 AF XY: 0.128 AC XY: 9491 AN XY: 74428

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0610

Gnomad4 FIN AF: 0.0603

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.156

Alfa AF: 0.151 Hom.: 2235

Bravo AF: 0.138

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.80

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: rs10511395; hg19: chr3-119536559;