11-47259902-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005693.4(NR1H3):c.155G>T(p.Gly52Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,611,938 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00078 ( 8 hom. )

Consequence

NR1H3
NM_005693.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.610

Publications

4 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032809675).

BP6

Variant 11-47259902-G-T is Benign according to our data. Variant chr11-47259902-G-T is described in ClinVar as [Benign]. Clinvar id is 779196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00652 (993/152278) while in subpopulation AFR AF = 0.0228 (948/41558). AF 95% confidence interval is 0.0216. There are 14 homozygotes in GnomAd4. There are 475 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 993 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1H3	NM_005693.4 link	c.155G>T	p.Gly52Val	missense_variant	Exon 3 of 10	ENST00000441012.7	NP_005684.2	Q13133-1B4DXU5F1D8N1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1H3	ENST00000441012.7 link	c.155G>T	p.Gly52Val	missense_variant	Exon 3 of 10	1	NM_005693.4	ENSP00000387946.2		Q13133-1

Frequencies

GnomAD3 genomes

AF:

0.00652

AC:

992

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0229

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00174

AC:

424

AN:

244366

AF XY:

0.00107

show subpopulations

Gnomad AFR exome

AF:

0.0243

Gnomad AMR exome

AF:

0.000995

Gnomad ASJ exome

AF:

0.000818

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000365

Gnomad OTH exome

AF:

0.000672

GnomAD4 exome

AF:

0.000776

AC:

1133

AN:

1459660

Hom.:

Cov.:

AF XY:

0.000629

AC XY:

457

AN XY:

726072

show subpopulations

African (AFR)

AF:

0.0266

AC:

889

AN:

33444

American (AMR)

AF:

0.00124

AC:

AN:

44522

Ashkenazi Jewish (ASJ)

AF:

0.000885

AC:

AN:

25986

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.0000465

AC:

AN:

86054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53202

Middle Eastern (MID)

AF:

0.00187

AC:

AN:

5356

European-Non Finnish (NFE)

AF:

0.0000378

AC:

AN:

1111190

Other (OTH)

AF:

0.00183

AC:

110

AN:

60230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

130

195

260

325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00652

AC:

993

AN:

152278

Hom.:

Cov.:

AF XY:

0.00638

AC XY:

475

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0228

AC:

948

AN:

41558

American (AMR)

AF:

0.00183

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68012

Other (OTH)

AF:

0.00520

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

103

155

206

258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000896

Hom.:

Bravo

AF:

0.00755

ESP6500AA

AF:

0.0175

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00203

AC:

246

Asia WGS

AF:

0.000866

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

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.16

CADD

Benign

1.2

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.097

T;.;.;T;T;.;.;.;.;.;T;T;T;T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.79

T;T;T;T;T;T;.;T;T;T;T;.;T;T;T;T

MetaRNN

Benign

0.0033

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.0

.;.;.;.;.;.;L;.;.;.;.;L;.;.;L;L

PhyloP100

-0.61

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.4

.;N;N;N;N;N;N;N;D;N;N;N;D;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.079

.;T;T;D;T;D;T;T;T;D;T;T;T;T;T;T

Sift4G

Benign

0.12

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.0

B;.;.;B;.;.;B;.;.;.;.;B;.;.;B;B

Vest4

0.15

MVP

0.64

MPC

0.56

ClinPred

0.0028

GERP RS

-0.83

PromoterAI

0.033

Neutral

(source)

Varity_R

0.041

gMVP

0.22

Mutation Taster

=98/2

polymorphism

(source)

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

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11-47259902-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over