rs55764158

Positions:

• chr3-119792528-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.-23+10228C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 998,920 control chromosomes in the GnomAD database, including 34,276 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 0.23 (5042 hom., cov: 32)
  • Exomes 𝑓: 0.25 (29234 hom.)
• Consequence: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.43

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]

PHB1P8 (HGNC:39287): (PHB1 pseudogene 8)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.-23+10228C>A		intron_variant		ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.95+9676C>A		intron_variant			NP_071285.1
NR1I2	NM_033013.3	c.-23+10228C>A		intron_variant			NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.-23+10228C>A		intron_variant		1	NM_003889.4	ENSP00000377319	P2
PHB1P8	ENST00000493810.1	n.700C>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35330 AN: 152000 Hom.: 5040 Cov.: 32

Gnomad AFR AF: 0.0823

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.251 AC: 212874 AN: 846802 Hom.: 29234 Cov.: 12 AF XY: 0.255 AC XY: 111386 AN XY: 437178

Gnomad4 AFR exome AF: 0.0684

Gnomad4 AMR exome AF: 0.479

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.339

Gnomad4 SAS exome AF: 0.295

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.245

GnomAD4 genome AF: 0.232 AC: 35338 AN: 152118 Hom.: 5042 Cov.: 32 AF XY: 0.233 AC XY: 17366 AN XY: 74378

Gnomad4 AFR AF: 0.0822

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.246

Alfa AF: 0.252 Hom.: 661

Bravo AF: 0.237

Asia WGS AF: 0.325 AC: 1129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.7
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs55764158; hg19: chr3-119511375; COSMIC: COSV61978804;