Variant 3-119811699-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003889.4(NR1I2):c.492T>C(p.Thr164=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 1,612,596 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 79 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 71 hom. )

Consequence

NR1I2
NM_003889.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.170

Variant links:

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]

NR1I2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 3-119811699-T-C is Benign according to our data. Variant chr3-119811699-T-C is described in ClinVar as [Benign]. Clinvar id is 775899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NR1I2	NM_003889.4 linkuse as main transcript	c.492T>C	p.Thr164=	synonymous_variant	4/9	ENST00000393716.8	NP_003880.3
NR1I2	NM_022002.3 linkuse as main transcript	c.609T>C	p.Thr203=	synonymous_variant	4/9		NP_071285.1
NR1I2	NM_033013.3 linkuse as main transcript	c.492T>C	p.Thr164=	synonymous_variant	4/9		NP_148934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1I2	ENST00000393716.8 linkuse as main transcript	c.492T>C	p.Thr164=	synonymous_variant	4/9	1	NM_003889.4	ENSP00000377319	P2	O75469-1
NR1I2	ENST00000337940.4 linkuse as main transcript	c.609T>C	p.Thr203=	synonymous_variant	4/9	1		ENSP00000336528	A2	O75469-7
NR1I2	ENST00000466380.6 linkuse as main transcript	c.492T>C	p.Thr164=	synonymous_variant	4/9	1		ENSP00000420297	A2	O75469-4
NR1I2	ENST00000493757.1 linkuse as main transcript	n.624T>C		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes

AF:

0.0176

AC:

2675

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0588

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.00456

AC:

1127

AN:

246910

Hom.:

AF XY:

0.00317

AC XY:

424

AN XY:

133560

show subpopulations

Gnomad AFR exome

AF:

0.0586

Gnomad AMR exome

AF:

0.00479

Gnomad ASJ exome

AF:

0.000301

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000152

Gnomad OTH exome

AF:

0.00232

GnomAD4 exome

AF:

0.00174

AC:

2541

AN:

1460302

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

1039

AN XY:

726260

show subpopulations

Gnomad4 AFR exome

AF:

0.0566

Gnomad4 AMR exome

AF:

0.00528

Gnomad4 ASJ exome

AF:

0.000422

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000932

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000141

Gnomad4 OTH exome

AF:

0.00385

GnomAD4 genome

AF:

0.0176

AC:

2682

AN:

152294

Hom.:

Cov.:

AF XY:

0.0170

AC XY:

1265

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0588

Gnomad4 AMR

AF:

0.0132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00408

Hom.:

Bravo

AF:

0.0199

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over