rs80320762

Positions:

• chr3-119807547-G-A

Variant summary

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

The NM_003889.4(NR1I2):​c.197+100G>A variant causes a intron 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: NR1I2 NM_003889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435

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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.197+100G>A		intron_variant		ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.314+100G>A		intron_variant			NP_071285.1
NR1I2	NM_033013.3	c.197+100G>A		intron_variant			NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.197+100G>A		intron_variant		1	NM_003889.4	ENSP00000377319	P2
NR1I2	ENST00000337940.4	c.314+100G>A		intron_variant		1		ENSP00000336528	A2
NR1I2	ENST00000466380.6	c.197+100G>A		intron_variant		1		ENSP00000420297	A2
NR1I2	ENST00000474090.1	n.485+100G>A		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.00789

Gnomad4 ASJ exome AF: 0.00433

Gnomad4 EAS exome AF: 0.0000277

Gnomad4 SAS exome AF: 0.000377

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000553

Gnomad4 OTH exome AF: 0.00897

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

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0131

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000661

Gnomad4 OTH AF: 0.0294

Alfa AF: 0.0266 Hom.: 19

Bravo AF: 0.0410

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs80320762; hg19: chr3-119526394;