Genetic Variant NR1I2:c.938-17C>T (chr3-119815306-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003889.4(NR1I2):c.938-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,605,040 control chromosomes in the GnomAD database, including 37,915 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 0.26 ( 5596 hom., cov: 32)

Exomes 𝑓: 0.20 ( 32319 hom. )

Consequence

NR1I2
NM_003889.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.184

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NR1I2	NM_003889.4 link	c.938-17C>T	intron_variant	Intron 6 of 8	ENST00000393716.8	NP_003880.3	O75469-1
NR1I2	NM_022002.3 link	c.1055-17C>T	intron_variant	Intron 6 of 8		NP_071285.1	O75469-7F1D8P9
NR1I2	NM_033013.3 link	c.827-17C>T	intron_variant	Intron 6 of 8		NP_148934.1	O75469-4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NR1I2	ENST00000393716.8 link	c.938-17C>T	intron_variant	Intron 6 of 8	1	NM_003889.4	ENSP00000377319.3	O75469-1J3KPQ3
NR1I2	ENST00000337940.4 link	c.1055-17C>T	intron_variant	Intron 6 of 8	1		ENSP00000336528.4	O75469-7
NR1I2	ENST00000466380.6 link	c.827-17C>T	intron_variant	Intron 6 of 8	1		ENSP00000420297.2	O75469-4H0Y8E2
NR1I2	ENST00000493757.1 link	n.1070-17C>T	intron_variant	Intron 3 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.255

AC:

38789

AN:

151938

Hom.:

5587

Cov.:

show subpopulations

Gnomad AFR

AF:

0.364

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.209

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.237

GnomAD3 exomes

AF:

0.239

AC:

60162

AN:

251252

Hom.:

8154

AF XY:

0.238

AC XY:

32269

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.365

Gnomad AMR exome

AF:

0.213

Gnomad ASJ exome

AF:

0.184

Gnomad EAS exome

AF:

0.465

Gnomad SAS exome

AF:

0.278

Gnomad FIN exome

AF:

0.258

Gnomad NFE exome

AF:

0.185

Gnomad OTH exome

AF:

0.224

GnomAD4 exome

AF:

0.201

AC:

291353

AN:

1452984

Hom.:

32319

Cov.:

AF XY:

0.203

AC XY:

146916

AN XY:

723460

show subpopulations

Gnomad4 AFR exome

AF:

0.375

Gnomad4 AMR exome

AF:

0.211

Gnomad4 ASJ exome

AF:

0.188

Gnomad4 EAS exome

AF:

0.461

Gnomad4 SAS exome

AF:

0.277

Gnomad4 FIN exome

AF:

0.256

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.222

GnomAD4 genome

AF:

0.255

AC:

38845

AN:

152056

Hom.:

5596

Cov.:

AF XY:

0.258

AC XY:

19179

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.364

Gnomad4 AMR

AF:

0.210

Gnomad4 ASJ

AF:

0.189

Gnomad4 EAS

AF:

0.474

Gnomad4 SAS

AF:

0.290

Gnomad4 FIN

AF:

0.267

Gnomad4 NFE

AF:

0.185

Gnomad4 OTH

AF:

0.236

Alfa

AF:

0.186

Hom.:

2993

Bravo

AF:

0.255

Asia WGS

AF:

0.359

AC:

1247

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.0

DANN

Benign

0.64

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over