rs80320762

Variant names:

• chr3-119807547-G-A
• rs80320762
• ENST00000648112.1:c.*320G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000648112.1(ENSG00000285585):​c.*320G>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 0.00901 in 1,035,834 control chromosomes in the GnomAD database, including 510 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 0.036 (329 hom., cov: 33)
  • Exomes 𝑓: 0.0044 (181 hom.)
• Consequence: ENSG00000285585 ENST00000648112.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435
• Publications: 3 publications found

Genes affected

ENSG00000285585 (HGNC:):

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]

NR1I2 Gene-Disease associations (from GenCC):

• pediatric lymphoma

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000648112.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1I2	NM_003889.4	MANE Select	c.197+100G>A		intron	N/A	NP_003880.3
	NR1I2	NM_022002.3		c.314+100G>A		intron	N/A	NP_071285.1
	NR1I2	NM_033013.3		c.197+100G>A		intron	N/A	NP_148934.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285585	ENST00000648112.1		c.*320G>A		3_prime_UTR	Exon 18 of 18	ENSP00000497876.1
	NR1I2	ENST00000393716.8	TSL:1 MANE Select	c.197+100G>A		intron	N/A	ENSP00000377319.3
	NR1I2	ENST00000337940.4	TSL:1	c.314+100G>A		intron	N/A	ENSP00000336528.4

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5443 AN: 152164 Hom.: 330 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000661

Gnomad OTH AF: 0.0297

GnomAD4 exome AF: 0.00439 AC: 3880 AN: 883552 Hom.: 181 AF XY: 0.00364 AC XY: 1671 AN XY: 459188

African (AFR) AF: 0.123 AC: 2731 AN: 22224

American (AMR) AF: 0.00789 AC: 305 AN: 38646

Ashkenazi Jewish (ASJ) AF: 0.00433 AC: 96 AN: 22158

East Asian (EAS) AF: 0.0000277 AC: 1 AN: 36078

South Asian (SAS) AF: 0.000377 AC: 27 AN: 71678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42010

Middle Eastern (MID) AF: 0.00389 AC: 12 AN: 3084

European-Non Finnish (NFE) AF: 0.000553 AC: 335 AN: 606108

Other (OTH) AF: 0.00897 AC: 373 AN: 41566

GnomAD4 genome AF: 0.0358 AC: 5448 AN: 152282 Hom.: 329 Cov.: 33 AF XY: 0.0335 AC XY: 2498 AN XY: 74458

African (AFR) AF: 0.123 AC: 5125 AN: 41526

American (AMR) AF: 0.0131 AC: 201 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000661 AC: 45 AN: 68036

Other (OTH) AF: 0.0294 AC: 62 AN: 2112

Alfa AF: 0.0313 Hom.: 25

Bravo AF: 0.0410

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs80320762; hg19: chr3-119526394;