Variant 11-47260473-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_005693.4(NR1H3):c.297C>T(p.Ser99Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,614,010 control chromosomes in the GnomAD database, including 40,082 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 ( 6319 hom., cov: 33)

Exomes 𝑓: 0.19 ( 33763 hom. )

Consequence

NR1H3
NM_005693.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.24

Variant links:

Genes affected

NR1H3 (HGNC:7966): (nuclear receptor subfamily 1 group H member 3) The protein encoded by this gene belongs to the NR1 subfamily of the nuclear receptor superfamily. The NR1 family members are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. This protein is highly expressed in visceral organs, including liver, kidney and intestine. It forms a heterodimer with retinoid X receptor (RXR), and regulates expression of target genes containing retinoid response elements. Studies in mice lacking this gene suggest that it may play an important role in the regulation of cholesterol homeostasis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

NR1H3 links:

NR1H3 (HGNC:):

NR1H3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP7

Synonymous conserved (PhyloP=-1.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1H3	NM_005693.4 linkuse as main transcript	c.297C>T	p.Ser99Ser	synonymous_variant	4/10	ENST00000441012.7	NP_005684.2	Q13133-1B4DXU5F1D8N1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1H3	ENST00000441012.7 linkuse as main transcript	c.297C>T	p.Ser99Ser	synonymous_variant	4/10	1	NM_005693.4	ENSP00000387946.2		Q13133-1

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39264

AN:

152034

Hom.:

6317

Cov.:

show subpopulations

Gnomad AFR

AF:

0.381

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.650

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.216

GnomAD3 exomes

AF:

0.256

AC:

64415

AN:

251222

Hom.:

11328

AF XY:

0.243

AC XY:

33033

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.382

Gnomad AMR exome

AF:

0.386

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.669

Gnomad SAS exome

AF:

0.230

Gnomad FIN exome

AF:

0.282

Gnomad NFE exome

AF:

0.149

Gnomad OTH exome

AF:

0.191

GnomAD4 exome

AF:

0.189

AC:

276775

AN:

1461856

Hom.:

33763

Cov.:

AF XY:

0.189

AC XY:

137212

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.382

Gnomad4 AMR exome

AF:

0.370

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.652

Gnomad4 SAS exome

AF:

0.238

Gnomad4 FIN exome

AF:

0.266

Gnomad4 NFE exome

AF:

0.153

Gnomad4 OTH exome

AF:

0.199

GnomAD4 genome

AF:

0.258

AC:

39278

AN:

152154

Hom.:

6319

Cov.:

AF XY:

0.268

AC XY:

19918

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.381

Gnomad4 AMR

AF:

0.272

Gnomad4 ASJ

AF:

0.131

Gnomad4 EAS

AF:

0.651

Gnomad4 SAS

AF:

0.240

Gnomad4 FIN

AF:

0.296

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.213

Alfa

AF:

0.170

Hom.:

3280

Bravo

AF:

0.265

Asia WGS

AF:

0.342

AC:

1186

AN:

3478

EpiCase

AF:

0.142

EpiControl

AF:

0.134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

6.8

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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