rs55764158

Variant names:

• chr3-119792528-C-A
• rs55764158
• NM_003889.4:c.-23+10228C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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:):

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003889.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	NM_003889.4	MANE Select	c.-23+10228C>A		intron	N/A	NP_003880.3
	NR1I2	NM_022002.3		c.95+9676C>A		intron	N/A	NP_071285.1	O75469-7
	NR1I2	NM_033013.3		c.-23+10228C>A		intron	N/A	NP_148934.1	O75469-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	ENST00000393716.8	TSL:1 MANE Select	c.-23+10228C>A		intron	N/A	ENSP00000377319.3	O75469-1
	ENSG00000285585	ENST00000648112.1		c.*2-14701C>A		intron	N/A	ENSP00000497876.1
	NR1I2	ENST00000337940.4	TSL:1	c.95+9676C>A		intron	N/A	ENSP00000336528.4	O75469-7

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

African (AFR) AF: 0.0684 AC: 1511 AN: 22088

American (AMR) AF: 0.479 AC: 16433 AN: 34322

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 4213 AN: 21362

East Asian (EAS) AF: 0.339 AC: 11034 AN: 32572

South Asian (SAS) AF: 0.295 AC: 20020 AN: 67840

European-Finnish (FIN) AF: 0.236 AC: 11069 AN: 46910

Middle Eastern (MID) AF: 0.211 AC: 838 AN: 3964

European-Non Finnish (NFE) AF: 0.239 AC: 138163 AN: 578544

Other (OTH) AF: 0.245 AC: 9593 AN: 39200

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

African (AFR) AF: 0.0822 AC: 3414 AN: 41542

American (AMR) AF: 0.353 AC: 5392 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 663 AN: 3468

East Asian (EAS) AF: 0.365 AC: 1883 AN: 5160

South Asian (SAS) AF: 0.306 AC: 1472 AN: 4810

European-Finnish (FIN) AF: 0.242 AC: 2561 AN: 10596

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19152 AN: 67946

Other (OTH) AF: 0.246 AC: 520 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.7
DANN	Benign	0.65
PhyloP100		3.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs55764158; hg19: chr3-119511375; COSMIC: COSV61978804;