dbSNP rs4752822: NR1H3:c.62-3690T>C (chr11-47256101-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001251934.2(NR1H3):c.62-3690T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,696 control chromosomes in the GnomAD database, including 11,759 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 0.38 ( 11759 hom., cov: 30)

Consequence

NR1H3
NM_001251934.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.85

Publications

8 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.05).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001251934.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
NR1H3	NM_001251934.2	c.62-3690T>C	intron	N/A	NP_001238863.1	B4DXU5
NR1H3	NM_001251935.2	c.62-3690T>C	intron	N/A	NP_001238864.1	B4DXU5
NR1H3	NM_001130102.3	c.-92-3690T>C	intron	N/A	NP_001123574.1	Q13133-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NR1H3	ENST00000616973.4	TSL:1	c.62-3690T>C	intron	N/A	ENSP00000477707.1	B4DXU5
NR1H3	ENST00000395397.7	TSL:1	c.-92-3690T>C	intron	N/A	ENSP00000378793.3	Q13133-3
NR1H3	ENST00000527464.5	TSL:1	n.283-3690T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57270

AN:

151578

Hom.:

11760

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.354

Gnomad ASJ

AF:

0.225

Gnomad EAS

AF:

0.745

Gnomad SAS

AF:

0.465

Gnomad FIN

AF:

0.427

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.326

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.378

AC:

57292

AN:

151696

Hom.:

11759

Cov.:

AF XY:

0.388

AC XY:

28723

AN XY:

74080

show subpopulations

African (AFR)

AF:

0.471

AC:

19464

AN:

41364

American (AMR)

AF:

0.353

AC:

5382

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.225

AC:

778

AN:

3460

East Asian (EAS)

AF:

0.745

AC:

3827

AN:

5134

South Asian (SAS)

AF:

0.465

AC:

2228

AN:

4794

European-Finnish (FIN)

AF:

0.427

AC:

4490

AN:

10510

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.298

AC:

20252

AN:

67906

Other (OTH)

AF:

0.322

AC:

675

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1717

3434

5151

6868

8585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

558

1116

1674

2232

2790

<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:

0.339

Hom.:

1164

Bravo

AF:

0.375

Asia WGS

AF:

0.542

AC:

1883

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.89

(source)

DANN

Benign

0.18

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over