3-119817728-G-T

Position:

• chr3-119817728-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003889.4(NR1I2):​c.*516G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00676 in 1,045,946 control chromosomes in the GnomAD database, including 27 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 0.0040 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0072 (26 hom.)
• Consequence: NR1I2 NM_003889.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS2: High Homozygotes in GnomAdExome4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1I2	NM_003889.4	c.*516G>T		3_prime_UTR_variant	9/9	ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3	c.*516G>T		3_prime_UTR_variant	9/9		NP_071285.1
NR1I2	NM_033013.3	c.*516G>T		3_prime_UTR_variant	9/9		NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8	c.*516G>T		3_prime_UTR_variant	9/9	1	NM_003889.4	ENSP00000377319	P2
NR1I2	ENST00000337940.4	c.*516G>T		3_prime_UTR_variant	9/9	1		ENSP00000336528	A2
NR1I2	ENST00000466380.6	c.*516G>T		3_prime_UTR_variant	9/9	1		ENSP00000420297	A2
NR1I2	ENST00000493757.1	n.1953G>T		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.00396 AC: 603 AN: 152108 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00689

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.00724 AC: 6467 AN: 893720 Hom.: 26 Cov.: 37 AF XY: 0.00721 AC XY: 2998 AN XY: 415820

Gnomad4 AFR exome AF: 0.000709

Gnomad4 AMR exome AF: 0.00203

Gnomad4 ASJ exome AF: 0.00680

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000339

Gnomad4 FIN exome AF: 0.00123

Gnomad4 NFE exome AF: 0.00771

Gnomad4 OTH exome AF: 0.00772

GnomAD4 genome AF: 0.00396 AC: 603 AN: 152226 Hom.: 1 Cov.: 33 AF XY: 0.00359 AC XY: 267 AN XY: 74424

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00689

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00213 Hom.: 1

Bravo AF: 0.00397

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.57
DANN	Benign	0.78

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: rs56147004; hg19: chr3-119536575;