dbSNP rs11039155: NR1H3:c.-6G>A (chr11-47259211-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_005693.4(NR1H3):c.-6G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,613,956 control chromosomes in the GnomAD database, including 19,103 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 0.12 ( 1470 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17633 hom. )

Consequence

NR1H3
NM_005693.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.71

Publications

42 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005693.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NR1H3	NM_005693.4	MANE Select	c.-6G>A	5_prime_UTR	Exon 2 of 10	NP_005684.2	F1D8N1
NR1H3	NM_001130101.3		c.-6G>A	5_prime_UTR	Exon 2 of 9	NP_001123573.1	Q13133-2
NR1H3	NM_001251934.2		c.62-580G>A	intron	N/A	NP_001238863.1	B4DXU5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NR1H3	ENST00000441012.7	TSL:1 MANE Select	c.-6G>A	5_prime_UTR	Exon 2 of 10	ENSP00000387946.2	Q13133-1
NR1H3	ENST00000467728.5	TSL:1	c.-6G>A	5_prime_UTR	Exon 1 of 9	ENSP00000420656.1	Q13133-1
NR1H3	ENST00000405853.7	TSL:1	c.-6G>A	5_prime_UTR	Exon 2 of 9	ENSP00000384745.3	Q13133-2

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17793

AN:

152066

Hom.:

1469

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0270

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.00557

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.279

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.152

Gnomad OTH

AF:

0.0938

GnomAD2 exomes

AF:

0.138

AC:

34597

AN:

251490

AF XY:

0.144

show subpopulations

Gnomad AFR exome

AF:

0.0254

Gnomad AMR exome

AF:

0.121

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.00163

Gnomad FIN exome

AF:

0.268

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.148

AC:

215765

AN:

1461772

Hom.:

17633

Cov.:

AF XY:

0.149

AC XY:

108534

AN XY:

727196

show subpopulations

African (AFR)

AF:

0.0216

AC:

724

AN:

33480

American (AMR)

AF:

0.122

AC:

5476

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

2683

AN:

26136

East Asian (EAS)

AF:

0.00229

AC:

AN:

39700

South Asian (SAS)

AF:

0.200

AC:

17223

AN:

86258

European-Finnish (FIN)

AF:

0.254

AC:

13554

AN:

53416

Middle Eastern (MID)

AF:

0.129

AC:

746

AN:

5768

European-Non Finnish (NFE)

AF:

0.150

AC:

167291

AN:

1111898

Other (OTH)

AF:

0.132

AC:

7977

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

10134

20268

30401

40535

50669

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5932

11864

17796

23728

29660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.117

AC:

17797

AN:

152184

Hom.:

1470

Cov.:

AF XY:

0.124

AC XY:

9237

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0269

AC:

1117

AN:

41558

American (AMR)

AF:

0.122

AC:

1861

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

365

AN:

3466

East Asian (EAS)

AF:

0.00559

AC:

AN:

5190

South Asian (SAS)

AF:

0.176

AC:

846

AN:

4814

European-Finnish (FIN)

AF:

0.279

AC:

2948

AN:

10560

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.152

AC:

10334

AN:

67980

Other (OTH)

AF:

0.0919

AC:

194

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

757

1514

2271

3028

3785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

210

420

630

840

1050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.126

Hom.:

2370

Bravo

AF:

0.0983

Asia WGS

AF:

0.0730

AC:

253

AN:

3478

EpiCase

AF:

0.137

EpiControl

AF:

0.131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

1.7

Mutation Taster

=300/0

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over